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  • 1
    ISSN: 1432-0827
    Schlagwort(e): Osteoporosis ; Histomorphometry ; Microradiography ; Osteodensitometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Quantitative histomorphometric and microradiographic analysis of iliac crest bone biopsy specimens of 10 unselected and untreated postmenopausal women with osteoporosis was performed and the results were correlated with the values measured by osteodensitometry on the right forearm. No positive correlation between histomorphometry or microradiography and osteodensitometry was observed. Moreover, the data of various histomorphometric parameters and those of the bone mineral content measured by microradiography revealed a significant negative correlation when compared to the values obtained by osteodensitometry. Our results suggest, that evaluation of one skeletal site is not necessarily representative of the entire skeleton in patients with postmenopausal osteoporosis.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    ISSN: 1432-0827
    Schlagwort(e): Photon absorptiometry ; Cortical bone density ; Bone index ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary An improved version of a previously described photon absorptiometry method for measuring the bone mineral content of the femoral shaft is presented. The study included 267 healthy persons, who served as control subjects, and 31 osteoporotic and 3 osteomalacic female patients. A monoenergetic source of241Am was used and a fully automatic apparatus designed. The examinations were recorded with an independent microcomputer and secondarily processed by the nuclear unit central computer. The guidelines of Cameron and West were used to perform various calculations from the initial absorption curve, and the clinical usefulness of these was tested. On the one hand, cortical bone density (CBD) and bone linear attenuation coefficient (BLAC) were found adequately to differentiate between osteoporotics and controls, but we defined a discriminative function (F) which allowed even better separation between the two groups. On the other hand, bone index (BI) was found to be the best parameter to follow an individual patient during therapy. These results underline the usefulness of these calculations for detecting and monitoring the progress of pathological states.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 34 (1982), S. 547-552 
    ISSN: 1432-0827
    Schlagwort(e): Rats ; Osteoporosis ; Anorganic ; Femur ; Castrate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The study describes the SEM appearances of endosteal and periosteal surfaces of anorganic femoral diaphyses from 16-month-old normal and castrate male rats. Different types of surfaces could be recognized in both groups. Percentage areas occupied by each surface type were analyzed with a Ladd Data Analyzing Digitizer. Endosteal surfaces were composed of significantly more (P〈0.05) incompletely mineralized, forming surface and significantly less (P〈0.05) completely mineralized, resting surface in castrates than in controls. Both endosteal and periosteal surfaces from experimental bone demonstrated significantly more (P〈0.05) osteoblast lucunae than did control surfaces, and vascular canal entrances were significantly wider (P〈0.001) on castrate endosteal surfaces than on control endosteal surfaces. There was a greater proportion of small nodule forming surface/large nodule forming surface in castrate endosteal bone than in control, and a greater proportion prolonged resting surface/fibrous resting surface in control periosteal bone than in castrate. The results indicate that, when viewed in the SEM, anorganic endosteal and periosteal bone surfaces from femoral diaphyses of old castrate male rats demonstrate appearances characteristic of changes in bone turnover that occur with osteoporosis.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    ISSN: 1432-0827
    Schlagwort(e): Osteoporosis ; Vertebral fracture ; Bone histomorphometry ; 85Sr
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The histologic heterogeneity of osteoporosis relative to normal controls has attracted great interest. There has been controversy as to whether patients with high turnover osteoporosis may convert to a normal or low turnover form, and vice versa. We have studied 44 patients over 12 years by dynamic histomorphometry and85Sr kinetics + calcium balance performed within 60 days in 20 patients (Group 1) and 75–808 days apart in the remainder (Group 2). In the first group, the histologic tissue level bone formation rate (BFR/BV or BFR/BS) was predictive of the85Sr measurements of bone formation (r=0.66P〈0.01). There was no statistically significant correlation in Group 2 and the regression coefficients were significantly different (P=0.01). Periodic regression was used to determine if seasonal changes were responsible for this loss of correlation; none was found that was of statistical significance. No systematic changes with time in bone formation were found in Group 2 during the period of observation; nor were consistent secular changes detected when the data for both groups were examined according to procedure data. In conclusion, bone formation may change with time in postmenopausal osteoporosis. Evidence that these changes are systematic was not found and this has implications for the design of treatment studies.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 52 (1993), S. 107-109 
    ISSN: 1432-0827
    Schlagwort(e): Osteoblastic cell lines ; Human osteosarcoma cell ; Aromatase ; Adrenal androgen ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Aromatase activity was studied in cultured human osteosarcoma cell (HOS). HOS was incubated from 12 to 72 hours with 10-10 M-10-5 M dexamethasone. Aromatase activity was determined by measuring [3H]H2O released upon the conversion of [1β-3H]androstenedione to estrone. HOS showed aromatase activity, and apparent km for [1β-3H]androstenedione was 4.46±0.98 nm (mean±SD). The aromatase activity was significantly increased by 10-9 M-10-5 M dexamethasone in a dose-dependent manner. Dexamethasone increased Vmax of aromatase activity but did not change its km value. These results suggest that osteoblastic cells have aromatase activity which is regulated by glucocorticoid, and directly convert androgen to estrogen in itself.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    ISSN: 1432-0827
    Schlagwort(e): Hip fracture ; Falls ; Osteoporosis ; Biomechanics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Hip fractures among the elderly are a significant and rapidly growing public health problem. The prevailing view is that most hip fractures are the consequence of age-related bone loss or osteoporosis. However, because over 90% of hip fractures are the result of falls, we have undertaken a falls surveillance study to determine if factors related to the mechanics of falling are associated with increased risk of hip fracture. Case subjects with hip fracture and control subjects without hip fracture were sampled from falls recorded at the Hebrew Rehabilitation Center for Aged, a chronic care facility. Fall information was obtained by interview of the subject and witnesses if the fall was witnessed. Data were analyzed by multiple logistic regression. Increased risk of hip fracture from a fall was associated with impacting on the hip or side of the leg and potential energy associated with the fall. Quetelet, or body mass index, was inversely related to fracture risk. The adjusted odds ratio of hip fracture for a fall involving impact on the hip region was 21.7 (95% confidence interval, 8.2–58). The potential energy associated with these falls was an order of magnitude greater than the average energy required to fracture elderly, cadaveric, proximal femurs in earlier in vitro experiments. We conclude, therefore, that a fall from standing height should no longer be considered minimal trauma but rather trauma of sufficient magnitude to pose a high risk of hip fracture if impact occurs on the hip and if energy-absorbing processes are inadequate. These new findings suggest that fall mechanics play an important role in the etiology of hip fracture among the elderly.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 52 (1993), S. 263-268 
    ISSN: 1432-0827
    Schlagwort(e): Osteoporosis ; Bone density ; Postmenopausal ; Vertebral collapse ; Bisphosphonate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Bone mineral density (BMD) at the lumbar spine, femoral neck, trochanteric region, and Ward's triangle was measured using dual-energy X-ray absorptiometry (DXA) in 118 women with osteoporotic vertebral collapse (average age 65 years), divided into four groups according to numbers and SD of vertebral deformation below norms: group 1:-3SD deformations only; group 2: one-4SD deformation; group 3: two-four-4SD deformations; and group 4: 5 or more-4SD deformations. There were no significant differences between the groups. Results were compared with those from 80 premenopausal (average age 32 years, range 20–40 years) and 109 postmenopausal normal women (average age 64, range 60–70 years). Mean BMD in osteoporotic group 1 was lower than premenopausal normal women by 32% at the lumbar spine, 31% femoral neck, 30% trochanteric region, and 44% at Ward's triangle, and postmenopausal controls by 17% lumbar spine, 16% femoral neck, 17% trochanter, and 14% Ward's triangle. There was a clear trend to reduction in mean BMD between osteoporotic groups 1 and 4 at all four measured sites with significant differences at the spine of 0.102 g/cm2 (P〈0.01) and Ward's triangle 0.059 g/cm2 (P〈0.01). When compared with premenopausal controls, there was a reduction in mean BMD between osteoporotic groups 1 and 4 of 10% at the lumbar spine, 7% femoral neck, 8% trochanteric region, and 13% Ward's triangle. Receiver operating characteristic analysis showed no significant differences in diagnostic sensitivities among the four measured sites for vertebral fractures. We conclude from this crosssectional data that the majority of bone loss in spinal osteoporosis occurs before the onset of fractures.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 52 (1993), S. 222-226 
    ISSN: 1432-0827
    Schlagwort(e): Growth hormone ; Osteoblast ; Growth factors ; Osteoporosis ; Bone cell cultures ; Bone formation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary In this study we investigated the direct, shortterm effects of human growth hormone (hGH) on the biology of normal adult human osteoblast-like (hOB) cells cultured from trabecular bone explants. In Subconfluent cultures, hGH stimulated hOB proliferation in a dose-dependent fashion (P〈0.001, n=15) with half-maximal effects at a concentration of 10 ng/ml. These mitogenic effects were detectable within 24 hours as shown by bromodeoxyuridine labeling. In confluent cultures containing mainly quiescent cells, hGH increased levels of alkaline phosphatase (P〈0.05, n=10) and to a lesser degree levels of procollagen type I carboxyterminal propeptide (PICP) (P=0.07, n=9). Effects on osteocalcin (bone GLa protein, BGP) levels were highly variable among different cell strains and only 7 of 10 cell strains showed a stimulatory response (P=0.16). We also studied the effects of hGH on osteoblastic production of insulin-like growth factor I (IGF-I) and IGF-II as well as the production of GH-dependent, insulin-like growth factor binding protein 3 (IGFBP-3). Under basal conditions, human osteoblasts produced IGF-II and IGFBP-3 in the conditioned medium. When stimulated with hGH, minor insignificant increase in both IGF-II and IGFBP-3 (125% and 126% of control, respectively) were detectable. No IGF-I was detectable in the conditioned medium under basal conditions or after stimulation with hGH. In conclusion, the results obtained in this study suggest that GH exerts direct anabolic effects on human osteoblasts.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 52 (1993), S. 239-243 
    ISSN: 1432-0827
    Schlagwort(e): Osteoporosis ; Exercise ; Ovariectomy ; Bone strength
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The effects of non-endurance exercise on bone properties were evaluated in 9-month-old sham-operated (SH) and ovariectomized (OVX) rats. The studies were started 3 months postsurgery, after bone mass was decreased in OVX rats. The sham and OVX rats were either kept sedentary (SED) or were trained to run with one of two protocols: 12 m/minute, 50 minutes/day, 4 days/week (low intensity, frequent, EX-1); or 21 m/minute, 40 minutes/day, 1 day/week (moderate intensity, infrequent, EX-2). A group of seven rats evaluated at the beginning of the study served as baseline control. The bone mineral was assessed by the ash weight of the left femur, tibia, and 4th lumbar vertebra. Biomechanical (strength, deformation, stress, strain, and stiffness) and morphometric (length, cortical and medullary area, moment of inertia) properties were evaluated for the right femur. There was a significantly lower bone mineral and mechanical properties in OVX-SED (n=7) than in SH-SED (n=10) rats. The OVX-EX-1 (n=6) rats had higher ash content of femur and tibia than OVX-SED rats, but the change was significant only for tibia. The EX-2 had no effect on the ash content, but femur stress was higher in OVX-EX-2 (n=8) than in OVX-SED rats. The femur yield force and deformation were improved in OVX rats with both exercise protocols, whereas the vertebra ash weight, femur strain, modulus of elasticity, length, cortical area, and moment of inertia were not changed. Non-endurance exercise did not affect bone properties in either SH-EX-1 (n=7) or SH-EX-2 (n=8) groups. We conclude that non-endurance exercise has beneficial effects on established osteopenia in ovariectomized rats.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 52 (1993), S. 244-247 
    ISSN: 1432-0827
    Schlagwort(e): Bone density ; Material damping ; Aging ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The aim of this work was a preliminary assessment of the feasibility of using in vivo measurements of mechanical properties of bones to detect mineral loss and further to relate them to the tendency of the bone to fracture in the case of loss of minerals, such as in osteoporosis. Previous studies of bone strength in vitro have demonstrated that the decrease in bone strength in both the spine and the femur has strong correlation with the mineral content (BMC) measured with bone densitometry. It was demonstrated that loss of mineral in the bone is accompanied by substantial change of the main mechanical properties, decrease of the Young's modulus, and increase of the damping factor. The change in those properties is one order of magnitude greater than the change in bone density. Moreover, increase of bone density, by was of training, resulted in decrease of the damping factor that also was substantially greater than the change in density. The tests showed clearly that the change in mechanical properties was much greater than the change in bone mass density. This offers an attractive new alternative to the detection of bone mass loss as it appears that the change of the bone mass is well correlated to the change in these mechanical properties. In particular, the change in the damping factor of the material was found to be much more substantial than the bone density change. Therefore, the damping mechanism offers the vehicle for a direct assessment of the bone tendency to fracture due to the loss of mass, as tendency to fracture and mass loss are known to be related. Increasing bone density due to training showed similar results. The decrease in damping, though still much greater than the increase in density, is not as much different as in the case of loss of mass because there is a point when density increases to the extent that the bone becomes compact (no voids) and its damping would not drop further with increasing mass. This method, as compared with the bone density measurement methods, appears to have some definite advantages for monitoring the mineral loss in bones.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 11
    ISSN: 1432-0827
    Schlagwort(e): Colles' fracture ; Hip fracture ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Objective: To determine the long-term risk of hip fracture following fracture of the distal forearm. Design: Registry-based cohort study comparing patients with a fracture of the distal forearm with a population-based cohort. Fracture cohort: All women and men above 40 years of age with a radiologically verified fracture of the distal forearm during a 5-year period. 1968–1972, in all 1,126 women and 212 men. Control cohort: An equal number of population-based, age-and sex-matched control persons selected from a population register. Measurements: All cohort members were followed up individually through record linkage until the first hip fracture, emigration, death, or the end of 1991. The cohort members contributed a total of 40,832 person-years of observation, and altogether 365 cases of hip fractures were observed. Results: Both women and men with a fracture of the distal forearm ran an increased risk of sustaining a subsequent hip fracture. The overall relative hazard for the women was 1.54 and for men 2.27. The increased risk in the women was independent of age at inclusion, but that in the men was more pronounced in the younger age groups. Conclusions: Patients with a fracture of the distal forearm run an increased risk of sustaining a subsequent hip fracture. They therefore appear to constitute a group in which appropriate prophylactic measures against osteoporosis and fractures should be considered.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 52 (1993), S. 331-333 
    ISSN: 1432-0827
    Schlagwort(e): Osteoporosis ; Nutrition ; Biochemical markers ; Crush fracture syndrome
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Thirty-six women with vertebral osteoporosis showed significantly decreased levels of biochemical markers of nutrition, transferrin (P〈0.001), prealbumin (P〈0.001), retinol binding-protein (P〈0.001), and fibronectin (P〈0.001), compared with 40 healthy women of similar age. Multiple regression analysis showed a significant (R2=0.509; P=0.0068) correlation between bone mineral content and biochemical markers of nutrition in the osteoporotic patients but not in the control group. These data suggest that postmenopausal osteoporosis may be associated with a nutritional deficiency.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 13
    ISSN: 1432-0827
    Schlagwort(e): Osteoporosis ; Menopause ; Estrogen ; Pyridinoline ; Bone resorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Objective: To evaluate and compare the effects or oral and transdermal estrogen replacement therapy on biochemical markers of bone resorption in early postmenopausal women Design: Controlled, randomized group comparison. Setting: Outpatient clinic for menopausal women and research into osteoporosis. Subjects: Sixty healthy women menopausal for less than 5 years and who had never received any medications interfering with bone metabolism. Interventions: The 60 women were randomly allocated to 3 months therapy with either oral conjugated estrogens (0.625 mg/day) (n = 28) or transdermal estradiol (50 jig/day) (n = 32) in cyclical combination with medroxyprogesterone acetate (5 mg/day). Main outcome measures: Traditional (urinary calcium/creatinine and hydroxyproline/creatinine) and the new specific (urinary pyridinoline/creatinine and deoxypyridinoline/creatinine) markers of bone resorption were determined before and after 3 months of treatment. Results: In both groups, circulating levels of estrone and estradiol were significantly (P 〈 0.001) increased during treatment. In women treated with oral conjugated equine estrogens, urinary calcium/creatinine and hydroxyproline/creatinine ratios were significantly (P 〈 0.05) reduced. Pyridinoline/creatinine ratio fell from 69.1 (4) [mean (SEM)] to 50 (4) μmol/μmol (P 〈 0.01) and deoxypyridinoline/creatinine ratio fell from 10.8 (1) [mean (SEM)] to 8.3 (0.8) μmol/μmol (P 〈 0.01). In the group treated with transdermal estradiol, urinary hydroxyproline/creatinine ratio was significantly (P 〈 0.05) reduced. Pyridinoline/creatinine ratio fell from 66.3 (4) [mean (SEM)] to 46.2 (3) μmol/μmol (P 〈 0.01) and deoxypyridinoline/creatinine ratio fell from 11.5 (1.5) [mean (SEM)] to 7.7 (0.6) μmol/μmol (P 〈 0.01). There were no differences between the evolution of the biochemical variables in the two groups. Conclusion: These results suggest that oral conjugated equine estrogens and transdermal estradiol, in the given doses, are equally effective in reducing postmenopausal bone resorption.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 14
    ISSN: 1432-0827
    Schlagwort(e): Osteocalcin ; Prednisolone ; Deflazacort ; Osteoporosis ; Plasma glucose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Glucocorticoids adversely affect bone and mineral metabolism through a number of mechanisms, including inhibition of bone formation. Deflazacort is a glucocorticoid which has been reported to be relatively “bone-sparing.” We compared the effects in oophorectomized sheep of deflazacort and prednisolone on the metabolism of osteocalcin (OC), a marker of osteoblast function. An [125I]OC infusion method was used to measure the OC plasma clearance rate (PCR) and OC plasma production rate (PPR). Six-day intravenous infusion of deflazacort and prednisolone (in the dose range 0.007–1.00 mg/hour) induced dose-dependent decreases in OC PPR which were of a similar pattern but significantly different magnitude (P 〈 0.02); deflazacort demonstrated a potency about 150% that of prednisolone. Both steroids decreased plasma OC levels on a dose-related basis but at the lower doses 0.05 mg/hour (P 〈 0.05) and 0.013 mg/hour (P 〈 0.0005), deflazacort caused greater decrements. OC PCR was significantly increased only by higher doses of deflazacort (1.00 mg/hour, 0.25 mg/hour;P 〈 0.05). Deflazacort and prednisolone increased both postabsorptive plasma glucose and plasma calcium levels, but there were no significant differences between their effects. We conclude that plasma OC levels and OC PPR in sheep were more sensitive to the effects of deflazacort than to prednisolone. At high doses, the depressive effect of deflazacort on plasma OC levels may have been due in part to an increased OC PCR which was not evident with prednisolone treatment. However, the agents appeared to have a similar dose-dependent hyperglycemic effect, and both caused a small dose-dependent increase in plasma calcium. These findings indicate that prednisolone had similarly potent effects on both bone and glucose metabolism while deflazacort exhibited differential potency on the two systems. The greater potency of deflazacort on bone in sheep may be due to species differences in steroid metabolism or steroid-receptor interaction.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. S68 
    ISSN: 1432-0827
    Schlagwort(e): Bone strain ; Fatigue failure ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Functionalin vivo strain data are examined in relation to bone material properties in an attempt to evaluate the relative importance of osteoporotic bone loss versus fatigue damage accumulation as factors underlying clinical bone fragility. Specifically, does the skeleton have a sufficiently large safety factor (ratio of bone failure strain to maximum functional strain) to require that fatigue damage accumulation is the main factor contributing to increased risk of fracture in the elderly? Existing methods limitin vivo strain measurements to the surfaces of cortical bone. Peak principal compressive strains measured at cortical sites during strenuous activity in various mammalian and avian species range from −1700 to −5200 με, averaging - 2500 με (−0.0025 strain). Much of this threefold variation reflects differences in the intensity of physical activity, as well as differences among species and bones that have been studied. Peak strains can also vary as much as tenfold at different cortical sites within the same bone. No data exist for cortical bone strain during strenuous activity in humans, but it is likely that human bones experience a similar range of peak strain levels. Compact bone fails in longitudinal compression at strains as high as −14,000 to −21,000 με, but begins to yield at strains between −6000 and −8000 με. Given that yielding involves rapid accumulation of microdamage within the bone, it seems prudent to base skeletal safety factors on the yield strain, rather than the ultimate failure strain of bone tissue. Safety factors to yield failure therefore range from 1.4 to 4.1. This safety factor range is likely diminished further by age-related increases in mineralization and secondary remodeling that reduce the strength and energy-absorbing capacity of bone. Although no one safety factor applies to all skeletal sites within an individual, it seems clear that osteoporotic bone loss of 40 to 50% of normal constitutes a causative factor of clinical bone fragility, particularly if bone loss is high at sites of high functional strain. Theoretical consideration of the statistical distribution of bone strength in relation to functional loading events within a population over a lifetime of use further supports this interpretation, by indicating an increased probability of fracture with increasing age. Fatigue damage accumulation will serve to exacerbate these trends. Bone loss and fatigue damage accumulation therefore, should be viewed as mutually reinforcing agents of bone fragility. Improved correlation of peak functional strain patterns with localized bone loss and bone turnover dynamics at sites of high fracture risk, together with assessment of microdamage, is needed to resolve the relative contribution of these factors to osteoporotic bone fragility.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. S143 
    ISSN: 1432-0827
    Schlagwort(e): icrocallus ; Cancellous bone ; Osteoporosis ; Osteoarthrosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Healing trabecular microfractures are a common feature in cancellous bone. These lesions, when observed in macerated cancellous bone slices, measure about 500 μm in diameter and surround fractures in trabeculae with microcallus. Whether microcallus is a structure acting primarily as a transient brace, preventing relative movement of the fragmented segments and enabling the trabecula to heal, or whether it is a permanent buttress reducing the stress on the fractured strut, preventing the healing process, is not known. Microfractures are the result of normal physical activity. Hence, the widespread occurrence of trabecular microfracture in cancellous bone implies that a reasonable rate of microfracture is physiologically tolerable. There are three putative effects for trabecular microfracture. One is that, in response to impulse loading, cancellous subchondral bone increases its rigidity due to osteosclerosis resulting from bone formed around microfractures. Another hypothesis is that, if sufficient trabecular microfractures occur, they will compromise the trabecular structure of the vertebra and the proximal femur leading to osteoporotic fracture. By inducing remodeling changes, microfractures have an effect on the maintenance of joint structure. There are two histological patterns for microfractures: an early stage, when actively forming woven bone is bridging the fracture; and a more common late stage, when woven bone is inactive. Femoral studies fail to demonstrate that an increasing number of healed or healing microfractures in osteoarthrosis causes the increase of bone in the head of femur. Only one study has reported a significant increase in the number of trabecular microfractures in osteoarthrotic femoral heads compared with normal controls. This significant increase was in patients taking antiinflammatory drugs. In osteoporotic fracture, sufficient trabecular microfracture may lead to femoral fracture. The bone loss in the vertebral bodies is by a loss of horizontal trabeculae. This loss reduces the resistance of vertical elements to deformation under load and creates the conditions for trabecular fracture. Coincident with this observation, microfracture is most prevalent on the vertical structure. The increase of microfractures with increasing age has three possible explanations: (l) the incidence of microfracture increases as trabeculae become thinner; (2) the incidence of microfracture is constant but the rate of healing decreases; or (3) these two factors combine to increase the number of microfractures. The occurrence of trabecular microfracture has been shown to correlate with factors such as physical activity, age, bone viability and remodeling potential, cancellous bone volume, bone mineral content, bone fatigue properties, and the direction of cancellous bone loading. As trabecular microfracture is not an event that initiates a pathological process, a number of important questions need to be addressed. Whatever the answers to these questions, trabecular microfracture is intimately linked to the nature of cancellous bone structure, and the conditions under which microfracture will compromise this structure are fundamental to the question of bone quality.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 17
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. 149-152 
    ISSN: 1432-0827
    Schlagwort(e): Ultrasound ; Bone mineral density ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary A new ultrasound bone densitometer has been developed that measures ultrasonic properties of the os calcis, namely, the speed of sound (SOS), broadband ultrasound attenuation (BUA), and a proprietary factor derived from SOS and BUA, termed “stiffness.” Short-term precision of ultrasound measurements was 1.4% for BUA, 0.2% for SOS, and 1.5% for stiffness in healthy women, and 1.1% for BUA, 0.1% for SOS, and 1.5% for stiffness in osteopenic women. One hundred seven women underwent measurements by ultrasound, together with dual energy X-ray absorptiometry (DXA) bone mineral density (BMD) measurements of the lumbar spine and proximal femur. Correlations between SOS, BUA, and stiffness measurements and DXA BMD measurements were all highly significant (P 〈 0.001) with r values varying from 0.54 to 0.67. BUA, SOS, and stiffness measurements were all significantly different between normal and osteopenic women even after adjusting for age, height, and weight (P 〈 0.05,P 〈 0.001, andP 〈 0.01, respectively). These results demonstrate that this ultrasound system measures ultrasonic properties of the os calcis with good precision, the measurements correlate moderately well with DXA BMD measurements and they can differentiate between normals and those with osteopenia.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 18
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. S151 
    ISSN: 1432-0827
    Schlagwort(e): Ultrasound ; Bone fragility ; Osteoporosis ; Fracture
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Progress in clinical characterization of bone relies on developing a means to clinically assessall of the important determinants of bone quality, specifically, the intrinsic material properties of a bone (stiffness and brittleness) versus the macroscopic structural properties [apparent mass density (g/cc), structural shape and distribution of cortical mass, trabecular architecture, extent of unrepaired microdamage, and defects associated with the accelerated remodeling in early menopause]. Ultrasound devices currently measure parameters related to either of only two basic properties: bone ultrasound attenuation (BUA) or the apparent velocity of wave propagation (AVU). Theory and repeated corroboration in the laboratory have shown that the velocity of sound in solids such as bone has a quantitative relationship to the elastic modulus (or stiffness) and mass density. Although no comparable physical model exists for BUA, growingin vitro andin vivo empirical evidence shows a relationship to stiffness and mass density as well. Therefore, the question of ultrasound's ability to provide additional, clinically useful information about bone quality reduces to this:Does bone quality depend significantly on bone stiffness and does stiffness depend on factors other than bone mass alone? Clinical study results provide mounting evidence of ultrasound's abilities. (1) Numerous studies compare either velocity or BUA with BMC or BMD. The correlation coefficients vary widely between studies, even when repeated by the same investigators and laboratories. Two studies demonstrated this by comparing groups of subjects who are indistinguishable by BMD at the lumbar spine, but whose mean AVU readings are significantly different. (2) Multiple studies of AVU and BUA by different investigators have shown the ability of ultrasound to distinguish, as effectively as BMC or BMD, women with osteoporotic vertebral crush deformities from normal women. Prospective studies have shown that AVU and BUA each indicated risk of future osteoporotic fractures. In a population-based, randomized, cross-sectional study of men and women, AVU discriminated between groups of subjects who had suffered low trauma fractures versus those free of fracture. Such repeated clinical evidence of the ability of BUA and AVU to detect bone fragility provides mounting evidence that ultrasound measures a clinically relevant property of bone quality in addition to and distinct from bone mass.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    Mycopathologia 121 (1993), S. 143-147 
    ISSN: 1573-0832
    Schlagwort(e): Electron microscopy ; Farmer's lung ; Saccharopolyspora rectivirgula ; Thermoactinomyces vulgaris
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The fine structure ofThermoactinomyces vulgaris andSaccharopolyspora rectivirgula is described by transmission electron microscopy. These two bacteria are the most common microbes causing farmer's lung. The fine structure of hyphae, germination of endospores and the details of conidial wall layers ofT. vulgaris, as well as the fine structure of septate hypha and globose, polygonal conidia ofS. rectivirgula are described. The conidial wall ofT. vulgaris consisted of an inner multilayered spore coat, intermediate spore coat and outer spore coat. The findings are important for the investigations to find fragments of these bacteria in the lungs of exposed patients and experimental animals.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 20
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 34 (1982), S. 519-522 
    ISSN: 1432-0827
    Schlagwort(e): Turner's syndrome ; Ovarian dysgenesis ; Osteoporosis ; Bone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The bone mineral status of 17 girls with Turner's syndrome was evaluated by single photon absorptiometry. Bone mineral content (BMC) was 25.4% below that predicted by normalization for age, sex, height, weight, and bone width. Only 25% of this demineralization could be attributed to delayed skeletal maturation. Bones of girls who received estrogen replacement therapy were less demineralized than those of the others. The bone mineral deficit became less pronounced with advancing age. It could not be determined if the apparent effect of estrogens was related to age or if the apparent improvement with age was really due to an effect of estrogen treatment. For 8 subjects followed longitudinally there was no significant change in the BMC deficit.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 21
    ISSN: 1432-0827
    Schlagwort(e): Male ; Osteoporosis ; Free testosterone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary It is unclear what proportion of the variance in bone density in elderly males is accounted for by testosterone status. We studied 112 ambulatory, elderly volunteers (mean age 71.7 years) and determined free testosterone (FT), as well as bone density measurements by photon absorptiometry at multiple sites. Our studies of 35 of these subjects 4 years later includedmorning FT and dual energy X-ray absorptiometry. There were no significant correlations between FT and bone density at multiple scanning sites with the effects of age partialed out. We suspect that our inability to detect a significant effect of FT on bone density was related to the relative strength of other determinants of bone density, as well as to the fact that FT values are far more dynamic than bone density.
    Materialart: Digitale Medien
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  • 22
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 52 (1993), S. 99-102 
    ISSN: 1432-0827
    Schlagwort(e): Bone density ; Osteoporosis ; Normal population
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Bone density of the spine and femoral neck and broadband ultrasound attenuation of the calcaneus were measured in 111 normal Spanish women between the ages of 30 and 70 years. The cross-sectional study showed that spine and hip density decreased by 36 and 29%, respectively, and the ultrasound attenuation value decreased by 32% between 30 and 70 years of age. The rate of bone loss at the three sites was significant in women over age 50 and in postmenopausal women. These normative data will be helpful in assessing bone mass in Spanish women suspected of having osteoporosis.
    Materialart: Digitale Medien
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 52 (1993), S. 344-347 
    ISSN: 1432-0827
    Schlagwort(e): Bone mineral measurement ; Osteoporosis ; Menopause
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The aim of our study was to compare the results provided by the measurement of vertebral and femoral bone mineral density (BMD) for assessing the individual risk of osteoporosis as defined by either low BMD and/or rapid bone loss. Vertebral and femoral BMD were measured twice at a mean interval of 21 months in 85 normal, early post-menopausal women who had passed a natural menopause 6 months to 3 years previously. According to the measurement site, 36% (spine), 29% (femoral neck), 35% (Ward's triangle), and 25% (trochanter) fall in the “at risk” category, defined by a BMD value of 1 SD or more below the normal values for premenopausal women. Based on vertebral BMD, 39–48% of the women at risk had a normal femoral BMD. On the other hand, 24–37% of the women classified at risk based on femoral BMD maintained a low risk at the vertebral level. The annual rate of bone loss was significantly greater for the Ward's triangle (-2.7±3.8%) and femoral neck (-2.1±2.5%) than for the spine (-1.5±2.1%) and trochanter (-1.5±3.4%). There was a significant relationship between the rate of loss measured at the spine and femoral levels (r=0.34–0.58). Among the 21 women with a rapid vertebral bone loss, 48–67% had a low bone loss at the femoral level and vice versa. The ratio between mean rate of loss and the precision of the measurement sites was greater for the spine (1.6) compared with the femur (1.1–0.71). Our results indicate that vertebral and femoral BMD measurements produce discordant results in assessing the individual risk for osteoporosis.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. 26-28 
    ISSN: 1432-0827
    Schlagwort(e): Calcitonin ; Calcitriol ; Calcium ; Densitometry ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Twenty-two middle-aged women with severe osteoporosis were treated for 2 years with either 0.5 mg of synthetic human calcitonin subcutaneously three times per week combined with 0.5 μg of calcitriol and 0.5 g of calcium per day orally or calcium only. The treatment with calcitonin plus calcitriol (12 patients) resulted in a significantly increased calcium absorption rate. The mean values for serum phosphate did not change during the treatment period and the mean values did not differ between the treatment groups, but the serum calcium and urinary Ca/Cr ratio increased somewhat in the group given the combined treatment. There was no evidence that the combined treatment improved the bone density in this study. It is possible that calcitriol, instead of increasing the effect of calcitonin by suppression of the parathyroid, might have counteracted its effect by increasing the bone resorption.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 25
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. S14 
    ISSN: 1432-0827
    Schlagwort(e): Stereology ; Morphology ; Osteoporosis ; Vertebral body
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Osteoporotic compression fractures of the spine differ from most other age-related fractures in that they usually are associated with minimal trauma and with loads no greater than those encountered during normal activities of daily living. With aging and osteoporosis, there is progressive resorption of bone, resulting in reductions in bone density, thinning of trabeculae, and loss of trabecular contiguity. These changes in trabecular bone structure are associated with losses in bone strength which are disproportionate to the reductions in bone mass alone. To explain this disproportionate loss of bone strength, the prevailing opinion is that density reductions in the vertebral centrum are accompanied by a reduction in the number of trabeculae, by preferential resorption of horizontal trabeculae, and by hypertrophy of the remaining vertical trabeculae. To evaluate this view of vertebral morphology, we performed three-dimensional stereological analysis of trabecular bone extracted from midsagittal sections of first lumbar vertebral bodies from 12 donors spanning an age of 27–81 years. We found that both the number (R2 = 0.63,P 〈 0.01) and thickness (R2 = 0.91,P 〈 0.01) of trabeculae decreased linearly with density (as expressed by bone volume fraction) whereas the spacing between the trabeculae (R2 = 0.61,P 〈 0.01) increased reciprocally. There were more vertical trabeculae with transverse trabeculae at all densities, and the number of vertical trabeculae changed with density at twice the rate of the number of transverse trabeculae (P 〈 0.001). These data do not support the prevailing view that there is preferential resorption of horizontal trabeculae or hypertrophy of the remaining vertical trabeculae. Bone density was also a strong (R2 = 0.90,P 〈 0.01) power law function of the ratio of trabecular thickness to mean intertrabecular spacing. From buckling theory, the critical buckling load of a trabecula is related to this ratio of trabecular thickness to effective length. The changes in trabecular morphology observed with decreasing bone density thus pose a “triple threat” to the strength and stability of vertebral trabecular bone, as not only are there fewer trabeculae, but the remaining trabeculae are both thinner and longer.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 26
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 34 (1982), S. 510-514 
    ISSN: 1432-0827
    Schlagwort(e): Rats ; Osteopenia of oophorectomy ; 1,25-Dihydroxyvitamin D3 ; Parathyroid hormone ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The effect of ovarian insufficiency on calcium metabolism has been thought to involve an increased bone resorptive effect of parathyroid hormone and possible impaired synthesis of 1,25-dihydroxyvitamin D3. In the present study a rat model allowing for controlled serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D3 was used. Oophorectomy in this species is associated with increased serum levels of 1,25-dihydroxyvitamin D3 and decreased bone mass. Although thyroparathyroidectomy increased bone mass, an increased sensitivity of bone to parathyroid hormone in oophorectomized rats was not observed. Thus the development of the osteopenia did not seem to be related to increased parathyroid hormone sensitivity or to reduced levels of 1,25-dihydroxyvitamin D3. Exogenous 1,25-dihydroxyvitamin D3 increased bone mass in oophorectomized as well as intact rats. Intestinal calcium transport was increased by moderate doses of 1,25-dihydroxyvitamin D3. Intestinal calcium transport was also reduced by thyroparathyroidectomy and increased by the administration of parathyroid extract. A tendency for increased accumulation of 1,25-dihydroxyvitamin D3 in blood in oophorectomized rats has been noted. It is suggested that the tendency to hypercalcemia in ovarian-insufficient females given 1-hydroxylated vitamin D compounds may be related to a diminished metabolism of 1,25-dihydroxyvitamin D3.
    Materialart: Digitale Medien
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  • 27
    ISSN: 1432-0827
    Schlagwort(e): Osteoporosis ; Glucocorticoids ; Rheumatoid arthritis ; Quantitative computed tomography ; Single photon absorptiometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The susceptibility to glucocorticoid-induced bone loss may vary in different parts of the skeleton. We studied 62 patients with rheumatoid arthritis, 26 of whom were on low-dose glucocorticoid treatment. Bone mineral content (BMC) in the forearm was measured by single photon absorptiometry at a cortical, diaphyseal, and at a mixed cortical and trabecular, metaphyseal site. Lumbar BMC was measured by dual energy computed tomography in a trabecular and a cortical region of interest. The presence of vertebral deformities was evaluated on lateral spine radiographs. After correction for possibly confounding variables, prednisone therapy significantly influenced BMC at both the trabecular (-22.0%, 95% confidence interval-36.0% to-8.1%) and cortical (-24.8%, 95% confidence interval-39.3% to-10.3%) lumbar site. A significant effect was also seen at the metaphyseal (-15.7%, 95% confidence interval-27.1% to-4.2%), but not the diaphyseal (-3.9%, 95% confidence interval-14.1% to 6.4%) site in the forearm. Correlations between peripheral and vertebral BMC were moderate at best. The diaphyseal to metaphyseal BMC ratio did not identify patients with vertebral osteoporosis. It is concluded that the anterior cortical rim of the vertebral body is more susceptible to the effects of glucocorticoids than the cortical bone in the forearm, and that measurements of trabecular and anterior cortical vertebral BMC are essential in the management of patients with possible glucocorticoid-associated osteoporosis.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 28
    ISSN: 1432-0827
    Schlagwort(e): Osteoporosis ; Biomechanics ; Bisphosphonates ; Bone resorption ; Aging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Alendronate (4-amino-1-bydroxybutylidene bisphosphonate) is a novel amino bisphosphonate that is being developed for the treatment of osteolytic bone disorders such as osteoporosis. As part of a 2-year carcinogenicity study, we investigated the morphologic and biomechanical effects of long-term alendronate (ALN) therapy, given throughout skeletal growth, maturation, and aging, on rat vertebrae and femora. Three treatment groups, receiving either deionized water, low- (1.00 mg/kg), or high-dose (3.75 mg/kg) ALN, were given daily oral treatment for 105 weeks. Results from mechanical tests indicate that ALN therapy (in males) increased the vertebral ultimate compressive load by 96% in the high- and 51% in the low-dose groups when compared with controls. ALN similarly increased the male ultimate femoral bending load by 59% in the high- and 31% in the low-dose groups. Vertebrae and femora from female rats treated with both high- and low-dose ALN also failed at significantly higher loads than controls, but no differences were seen between low- and high-dose groups. Morphologic analysis of both male and female vertebrae revealed a dose-dependent increase in area fraction of bone. Rats receiving high-dose ALN had a greater area fraction of bone than those receiving low doses. Both groups were greater than controls. Thus, the administration of ALN resulted in increased femoral cortical bending load when compared with control animals, as well as increased vertebral ultimate compressive load commensurate with a dose-related preservation of vertebral bone. We therefore conclude that long-term ALN treatment preserves the structural and morphologic properties of both cortical and trabecular bone in rats and, with further study, may provide a valuable alternative to current therapy for the treatment of osteoporosis.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. S7 
    ISSN: 1432-0827
    Schlagwort(e): Bone density ; Fractures ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary New technology for noninvasive measurement of bone mass has enabled many studies of bone mass and its relationship to fracture, which challenge the view that bone mass is the only relevant factor in the etiology of fractures. Several studies have reported ROC curves that generally show values of about 80%. No convincing evidence suggests that one technique is superior to another. The reported relative risks or odds ratios for a fracture usually range between 1.2 and 2.5 per SD. There is no doubt that the risk of a fracture increases as the bone density decreases. However, even with a low bone mass, the risk ofnot fracturing a bone over the next year is over 90%. Most of the data suggest that patients with severe vertebral fractures have lower bone mass than those with mild fractures, but some women with similarly low bone mass have mild or no fractures. The weight of the evidence suggests that age has an effect on fracture incidence which is independent of bone mass. Trauma is such a major factor that it is surprising to find almost no studies that have controlled for it. The relationship between bone mass and bone failure is strong, but other factors must also be contributing to the bone failure which, like heart failure or renal failure, is a complex, multifactorial disease.
    Materialart: Digitale Medien
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 52 (1993), S. 90-93 
    ISSN: 1432-0827
    Schlagwort(e): Metabolic bone disease ; Tumors ; Paget's disease ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Forty-three patients were treated for a total duration of 301 patient-years with calcitonin (CT) (range 3–16 years, median duration 6 years 6 months). Eighty-four percent of patients were suffering from complications associated with Paget's disease and the remainder from osteoporosis. In the majority of patients, CT was administered by the subcutaneous route and one patient was psychologically dependent on calcitonin injections. There were no long-term side effects associated with CT therapy. In a separate group of 105 patients consisting of 83 patients on human CT and 22 patients on salmon CT, injections showed short-term side effects in 77% and 64% of these patients, respectively (NS). Side effects associated with nasally administered salmon CT in 25 patients were mild and of low incidence (32%). Long-term administration of calcitonin in humans is safe and devoid of any serious or long-term side effects.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 52 (1993), S. 130-138 
    ISSN: 1432-0827
    Schlagwort(e): Fluoride ; Bone ; Osteoporosis ; Bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary A mathematical model was developed that prediets fluoride accumulation and clearance from the skeleton based upon fluoride bioavailability, bone remodeling rate, and the fluoride binding characteristics of bone. It was assumed that fluoride binds to bone in a nonlinear fashion such that a smaller percentage of fluoride is bound to bone if fluoride intake is increased to high levels. Bone resorption rate was assumed to be proportional to the solubility of hydroxyfluorapatite which is inversely related to bone fluoride content. The predictions made by the model compared favorably with experimental results from fluoride uptake and clearance studies. Parametric studies done using the model showed the following: (1) fluoride can be cleared from the skeleton by bone remodeling, but fluoride clearance takes over four times longer than does fluoride uptake; and (2) fluoride uptake by the skeleton was positively associated with bone remodeling rate. However, the concentration of fluoride in newly formed bone does not decrease with reduced remodeling rates and surpasses 10,000 ppm for intakes of fluoride greater than 9 mg/day. For osteoporosis, daily dose and duration of fluoride treatment should be selected to avoid reaching a toxic cumulative bone fluoride content.
    Materialart: Digitale Medien
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  • 32
    ISSN: 1432-0827
    Schlagwort(e): Vitamin D ; Calcitriol ; Osteoporosis ; Femoral Fracture
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary In a previous study we were able to show that in women over the age of 45 the level of 1,25-dihydroxyvitamin D (1,25(OH)2D) in bone, but not in serum, is significantly reduced when compared with younger women. In the present study we measured the concentration of 1,25(OH)2D in sera and bones of 19 female patients with subcapital fractures of the femur, mean age 78±2 years. We were able to show that serum levels of 1,25(OH)2D were within the normal range, while bone levels were markedly reduced compared to levels in femoral bone obtained from young female cadavers or to the previously reported levels in non-osteoporotic elderly women. Thus, reduced levels of 1,25(OH)2D in bones of elderly women may lead, together with other factors, to subcapital fractures.
    Materialart: Digitale Medien
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  • 33
    ISSN: 1432-0827
    Schlagwort(e): Early postmenopause ; Vertebral bone mass ; Combined regimen ; Calcitonin ; Estrogen ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The study was carried out to determine the effect of a combination regimen of a small dose of calcitonin added to conjugated estrogens with medroxyprogesterone acetate on vertebral bone mass in early postmenopausal women. Comparisons were made with groups of women on calcitonin alone, on conjugated estrogens with medroxyprogesterone acetate alone, or on no treatment. The study was carried out over a 2-year period. The results of the study suggest that the combined regimen of calcitonin and estrogens increased vertebral bone mass in early postmenopausal women to a greater extent than calcitonin alone or estrogen alone. Increases in vertebral bone mass of 11.2% after 1 year and 9.2% after 2 years were demonstrated using the combined regimen. Both estrogens alone and calcitonin alone were, however, very effective in preventing rapid bone loss in the postmenopausal women studied.
    Materialart: Digitale Medien
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  • 34
    ISSN: 1432-0827
    Schlagwort(e): Chondrocytes ; High-density suspension culture ; Electron microscopy ; Matrix vesicle ; Apatite formation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Chondrocyte cultures grown in centrifuge tubes with intermittent centrifugation differentiate into hypertrophic chondrocytes and form calcification. We examined chondrocytes cultured in this system electron microscopically. Rat growth-plate chondrocytes were seeded in a plastic centrifuge tube and cultured in the presence of Eagle's minimum essential medium supplemented with 10% fetal bovine serum and 50 μg of ascorbic acid per ml. Specimens were examined by using electron microscopy and selected-area electron-diffraction techniques. In the early stage of culture, a few chondrocytes were scattered and extracellular matrices were not observed. In the middle stage of the cultures, the chondrocytes resembled proliferative cells. Matrix vesicles appeared to be budding from the cell surfaces of chondrocytes and were observed sparsely in the extracellular matrices, which were well formed around the chondrocytes. Matrix vesicles increased substantially during the following cultures. In the mature stage of the cultures, crystal formation related to matrix vesicles was observed. In the 33-day cultures, several masses of calcified matrix were formed and it was confirmed to be apatite by selected-area electron diffraction analysis. The chondrocytes appeared hypertrophic during this same stage. The 56-day culture was similar to the 33-day culture. It was concluded that this culture system provides an extracellular-matrix mineralization which is produced by chondrocytes per se.
    Materialart: Digitale Medien
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. 225-228 
    ISSN: 1432-0827
    Schlagwort(e): Osteoporosis ; Hormone replacement therapy ; Menopause ; Bone density
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary The purpose of this study was to determine whether bone mineral density (BMD) measurements at the lumbar spine and femoral neck provided comparable information to women planning to use that knowledge to help them make a decision about hormone replacement therapy. Eighty-eight healthy Caucasian women, aged 44–59 and within 0 to 5 years of menopause, participated in the study. BMD measurements were performed at the lumbar spine (L1-L4) and the femoral neck by dual energy X-ray absorptiometry (DXA). Criteria suggested by the National Osteoporosis Foundation were used to categorize women as “at risk” for osteoporosis, bone density more than one standard deviation (SD) below the young adult mean, or as “low risk”, bone density at or above this level. The re that 46 women would be classified into the low risk category on the basis of spinal BMD alone. However, 28 of these 46 women would fall into the at risk category when the femoral neck BMD was measured. Sixty-one percent of women informed they were at low risk on the basis of spinal BMD would be considered at risk based on femoral neck BMD. When femoral neck BMD was used as the primary risk indicator, 14% of the women classified as low risk would be at risk if spinal BMD were added. These results suggest that both lumbar spine and proximal femur measurements should be made when women are using bone density measurements as an aid in deciding whether or not to use hormone therapy in their postmenopausal years.
    Materialart: Digitale Medien
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  • 36
    ISSN: 1432-0827
    Schlagwort(e): Bone mass ; Bone density ; Osteoporosis ; Muscle training ; Exercise
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary On the premise that bone response to exercise is locally controlled [1], we conducted a randomized trial to evaluate the effects of a 1-year training of psoas muscles (treatment group: TG) versus a 1-year training of deltoid muscles (control group: CG) on the lumbar trabecular bone mineral density (TBMD). TBMD was measured with computed tomography scan. Seventy-eight subjects were included and 67 completed the study. Intention to treat analysis revealed no significant change in TBMD from 0 to 12 months. Data analysis in the 67 remaining women, including both assiduous and nonassiduous subjects, revealed greater bone loss in CG than in TG although the difference was not significant. Similar analysis in a subgroup of subjects who performed the exercises assiduously (TG: n = 23, CG: n = 26) showed that the mean bone loss of all four vertebrae from 0 to 12 months was significantly greater in the CG (−8.87 ± 12.75 mg/cm3, mean ± SD) than in the TG (0.14 ± 11.21 mg/cm3, mean ± SD,P = 0.01). These results suggest that continuous 1-year psoas training can prevent lumbar bone loss in postmenopausal women and support the hypothesis of local action of physical activity.
    Materialart: Digitale Medien
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  • 37
    ISSN: 1432-0827
    Schlagwort(e): Cancellous bone ; Bone strength ; Osteoporosis ; Trabecular bone quality
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary This paper discusses two novel applications of nuclear magnetic resonance (NMR) as an investigational tool for the assessment of cancellous bone microarchitecture. It further outlines extensions of the method forin vivo clinical evaluation of bone strength in patients with skeletal disorders such as osteoporosis. The first method relies on the hypothesis that the presence of two phases of different magnetic permeability, i.e., bone and bone marrow, causes a spatial nonuniformity of the magnetic field across the measurement volume. The resulting spread in resonance frequency shortens the decay time constant (T2*) of the time domain proton signal in bone marrow or its substitute (water). Increased trabecular spacing, such as it occurs in osteoporosis, reduces the spatial field inhomogeneity and thus prolongs T2*, which has been shown bothin vitro andin vivo. Subjects with osteoporosis, characterized by either low bone mineral density and/or spine compression fractures, have T2* values that are significantly prolonged. The second method focuses on a direct measurement of micromorphometric parameters of cancellous bone, using the principles of proton NMR microscopy in conjunction with computer processing of the resulting digital images. Image contrast between the trabeculae and the intertrabecular space is based on the marrow protons providing a signal, as opposed to bone, which appears with background intensity. Once tissues have been classified (into bone and marrow), for example, by means of a histogram-based segmentation algorithm, bone area fraction, mean trabecular plate density (MTPD), and mean trabecular plate thickness (MTPT) can be computed without the need for further operator intervention. The most critical parameter for successful implementation is image slice thickness which determines the extent of partial volume blurring. At 400 MHz spectrometer frequency (9.4 T field strength), images of appropriate resolution can be obtained from a 1 cm3 specimen of vertebral cancellous bone in 1 hour or less. It is shown that for relatively isotropic cancellous bone such as the one found in the vertebrae, a slice thickness on the order of 200 μm is adequate, with an inplane resolution on the order of 50 × 50 μm2 As an illustration of the technique, the relationship among the different stereologic parameters in cadaver specimens of human lumbar vertebrae is reported, showing a strong association between the area fraction and both MTPD and MTPT. The chief benefit of the new technique is its nondestructive nature and its ability to provide histomorphometric images from multiple physical locations and in multiple planes, which is desirable because of the large spatial variations in the morphologic parameters within the bone. Finally, the technique is demonstrated to be potentially also noninvasive, as illustrated with images from the human finger, acquired on a modified 1.5 Tesla clinical magnetic resonance imaging system at a pixel size of 95 × 95 μm2
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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. S23 
    ISSN: 1432-0827
    Schlagwort(e): Osteoporosis ; Epidemiology ; Hip fracture
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Fragility fractures, particularly those of the hip, vertebrae, and distal forearm, constitute a major public health problem. The two ultimate determinants of fracture are bone strength and propensity to trauma. Bone strength depends not only upon bone mass but also upon a variety of qualitative aspects of bone structure. These include its architecture, the amount of fatigue damage it has sustained, and changes in its bulk material properties, indices that are collectively subsumed into the term “bone quality” Fragility fractures show differences in their patterns of incidence by age, sex, ethnic group, geographic area, and season. Many of these differences are currently unexplained, and disorders of bone quality might contribute to them. There are two fracture sites at which evidence implicates bone quality more directly—the spine and proximal femur. Many vertebral compression fractures follow minimal trauma, and controlled studies suggest that vertebral microarchitecture contributes to fracture risk independently of vertebral bone mass. At the hip, observational studies have pointed to a role for disordered trabecular architecture, accumulation of microfractures (fatigue damage), and the accumulation of osteoid. The extent to which these phenomena act independently of bone mass, however, remains uncertain.
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  • 39
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. S157 
    ISSN: 1432-0827
    Schlagwort(e): Ultrasound ; Biomechanical competence ; Bone strength ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary Ultrasound has been investigated as a tool for characterizing the biomechanical competence of bone. The rationale for using ultrasound rests on two points. First, its interaction with tissues can be used to measure their density, velocity, and structure, and thus to characterize the elasticity and to infer the strength of bone. Second, ultrasound may be used to characterize tissue properties over a wide range of spatial dimensions and organizational levels, ranging from its constituents (e.g., trabeculae for cancellous bone) to the entire organ. Different ultrasound techniques can be used to investigate diverse bone properties, but two techniques have emerged as having the potential for providing useful information on problems of current biomedical interest. These measure two parameters, density and velocity, which correlate with the elastic and ultimate properties of bone. In particular, the elasticity E is formally related to the product of density and velocity squared, E = ϱv2. Moreover, it has been shown by mechanical testing that there is a single linear correlation between elasticity and strength at all orientations, both in cortical and in cancellous bone, materials with a strong intrinsic anisotropy. At the tissue level, it may therefore be expected that the ultrasound parameters will prove to be useful predictors of bone strength and of its dependence on orientation.In vitro ultrasound studies have shown that these properties can be measured specifically and quantitatively, and that they vary under different physiological conditions.
    Materialart: Digitale Medien
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  • 40
    Digitale Medien
    Digitale Medien
    Springer
    Calcified tissue international 53 (1993), S. S75 
    ISSN: 1432-0827
    Schlagwort(e): Microdamage ; Remodeling ; Fatigue ; Osteoporosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Physik
    Notizen: Summary This paper reviews the direct and indirect evidence for and against the idea that bone remodeling repairs fatigue damage. It defines experiments that should be performed to determine whether the accumulation and repair of fatigue damage is relevant to the pathogenesis of osteoporotic fracture. The experimental evidence favors the hypothesis that microdamage evokes local remodeling. The data suggest that the balance between the microdamage burden and bone repair is nearly constant. The indirect evidence comes from clinical observations that show positive relationships between depressed bone formation rate or prolonged remodeling period with bone fracture. More compelling indirect evidence comes from studies in which bone remodeling was pharmaceutically depressed, and fracture incidence rose in direct proportion. Data on microdamage accumulation were not collected in these studies. Conversely, some experimental evidence disputes a direct relationship between fatigue microdamage and repair. In these studies, increased amounts of bone microdamage in hyperadrenocortical dogs, and in irradiated dogs, could not be demonstrated even though bone fragility increased without associated osteopenia. Finally, the indirect evidence that argues that microdamage does not initiate repair is based on inference and does not provide an adequate test of the hypothesis. In balance, the current body of evidence favors the contention that bone remodeling repairs fatigue damage and thereby prevents fracture. Future studies should verify that microdamage accumulates when bone fracture occurs in conjunction with depressed remodeling activation frequency.
    Materialart: Digitale Medien
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  • 41
    ISSN: 1432-1041
    Schlagwort(e): Liver cirrhosis ; Spirapril ; ACE inhibitor ; pharmacokinetics ; haemodynamic effects ; liver function tests
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensinconverting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n=10), in patients with chronic, non-cirrhotic liver disease (n=8) and in a control group of healthy subjects (n=16). The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 μg·h·l−1, 923 μg·h·l−1 and 1300 μg·h·l−1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively. Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h−1 in patients vs. 2.00 h−1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls. Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients.
    Materialart: Digitale Medien
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  • 42
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 357-361 
    ISSN: 1432-1041
    Schlagwort(e): Circadian rhythms ; Indomethacin ; Ketoprofen ; pharmacokinetics ; time-varying models ; nonsteroidal anti-inflammatory drugs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A one-compartment model with first-order absorption has provided good fits to five sets of indomethacin data and four sets of ketoprofen data taken at different times of day. There was substantial variation in the model parameters with time of administration and most of the features of this variation applied equally to both drugs. From the data examined, the source of variation appears to be mainly in the absorption phase and this was confirmed using a chronokinetic analysis, in which simultaneous fits were obtained with time-variant rate parameters. However, there may also be circadian variation in protein binding. The danger of quoting parameter values for either of these two drugs based on administration at a single time of day has been illustrated, and this may well be true for other drugs.
    Materialart: Digitale Medien
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  • 43
    ISSN: 1432-1041
    Schlagwort(e): Gamma-hydroxybutyric acid ; pharmacokinetics ; dose-proportionality
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg−1. The AUC increased disproportionately with the dose and so the apparent oral clearance decreased significantly as the dose was increased, whereas the terminal half-life and mean residence time increased. The peak plasma concentrations normalised to the lowest dose fell significantly with increasing doses, whilst the corresponding peak times increased. These findings suggest that both the oral absorption and the elimination of GHB are capacity-limited processes. GHB did not bind to significant extent to plasma proteins over the therapeutic concentration range. The pharmacokinetic parameters in healthy volunteers were not significantly different from those previously observed in alcohol-dependent patients with compensated alcoholic liver disease.
    Materialart: Digitale Medien
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  • 44
    ISSN: 1432-1041
    Schlagwort(e): Glyceryl trinitrate spray ; pharmacokinetics ; a/b-ratio ; pulmonary artery diastolic pressure ; finger pulse curve ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The time course and the magnitude of the effect of glyceryl trinitrate (GTN) on central venous (pulmonary artery diastolic pressure-PAPd) and peripheral arterial (a/b-ratio of the finger pulse wave) haemodynamics were compared in a randomized double-blind cross-over study in 12 patients suffering from congestive heart failure (NYHA II–III) with elevated PADd at rest (≥15 mm Hg). The data were obtained in a bioavailability study of two sprays of glyceryl trinitrate, which differed in their galenical characteristics and in the dose of GTN (0.4 mg vs. 0.8 mg). Following sublingual administration of each spray, PAPd, a/b-ratio and the plasma concentrations of GTN and its metabolites were measured up to 30 min. The relative bioavailability of GTN of the test preparation was estimated to be 157%, 161% and 147%, when calculated from the plasma concentration-time data or the integrated effect of GTN on a/b-ratio or PAPd, respectively. The mean time courses of the decrease in PAPd and the increase in the a/b-ratio of the finger pulse curve were mirror images. Thus, there was a strong correlation between the mean values of PAPd and a/b-ratio following the administration of glyceryl trinitrate. Since the slope of the relationship differed considerably between the patients, the magnitude of effect of GTN on PAPd in the individual patient could not be predicted from the changes in a/b-ratio.
    Materialart: Digitale Medien
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 463-466 
    ISSN: 1432-1041
    Schlagwort(e): Benazepril ; Proteinuria ; benazeprilat ; ACE inhibitor ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have investigated whether the pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril hydrochloride are altered with proteinuria by studying 8 patients with major proteinuria of different causes who were given a single dose of 10 mg p.o. The maximum plasma concentration of benazepril was found between 0.5 and 2 h after dosing (median 1 h). Its elimination was almost complete within 6 h. Peak plasma levels of benazeprilat, the active metabolite of benazepril, were observed between 1 and 6 h (median 2.5 h). The elimination of benazeprilat from plasma was biphasic, with mean initial and terminal half-lives of 3.0 and 17.3 h, respectively. On average, the pharmacokinetic parameters of benazepril and benazeprilat in the patients did not differ from those in a historical control group of healthy volunteers, but intersubject variability in the AUC and half-lives of benazeprilat was greater in the patients. Plasma ACE was completely inhibited from 1.5 to 6 h after dosing, and at 48 h the mean inhibition was still 42 %. Plasma renin showed substantial intersubject variation. Mean supine blood pressure (systolic/diastolic) was reduced from baseline by a maximum of 18/13 mm Hg at 6 h. Proteinuria was diminished after benazepril in 7 patients. In conclusion, the results of this study suggest that proteinuria in the nephrotic range does not require a change in benazepril dosage.
    Materialart: Digitale Medien
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  • 46
    ISSN: 1432-1041
    Schlagwort(e): dDAVP ; bioavailability ; gastrointestinal tract ; healthy volunteers ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP) from different regions of the gastrointestinal (GI) tract (stomach, duodenum, jejunum, ileum, colon, rectum) has been studied in 6 healthy, male volunteers aged 24 to 35 years, followed for 12 h after each drug administration. For i. v. administration the subjects received 4 μg dDAVP. For intestinal administration 400 μg dDAVP was directly applied to six distinct sites in the GI tract via two or four channel tubes with or without a distal occlusive balloon. Biological effects were assessed and plasma and urinary levels of dDAVP were measured using a specific, sensitive RIA. Urine osmolality remained elevated and diuresis decreased for 12 h following dDAVP administration irrespective of the site of application. After i. v. administration, the half-life of elimination of dDAVP was 60.0 min, plasma clearance 1.7 ml·min−1·kg−1, amount excreted in urine 2.0 μg and renal clearance was 0.8 ml·min−1·kg−1. The mean bioavailability (f) after gastric application was 0.19% (range 0.02–0.35%). f was 0.24% after duodenal application (range 0.04–0.62%), 0.19% after jejunal (range 0.01–0.41%), 0.03% after distal ileal (range 0.01–0.08%), 0.04% after proximal colonic (range 0.01–0.12%) and 0.04% after rectal (0.01–0.10%) application. The bioavailability was significantly higher in the three upper GI regions in comparison to the three lower regions. The bioavailability of dDAVP after gastric, duodenal and jejunal application was similar to that after swallowing a tablet in a previous study. Absorption from the ileum was lower than expected and no preferential site of absorption was found.
    Materialart: Digitale Medien
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 247-251 
    ISSN: 1432-1041
    Schlagwort(e): Proguanil ; Pregnancy ; Malaria ; cycloguanil ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma and whole blood concentrations of proguanil, its active metabolite cycloguanil, and the inactive metabolite 4-chlorophenyl-biguanide, were measured by HPLC in 10 healthy Karen women in the last trimester of pregnancy, following a 200 mg single oral dose of proguanil. Four of these women were restudied 2 months after delivery. The pharmacokinetic properties of proguanil were similar during and after pregnancy. Median peak plasma concentrations of proguanil during pregnancy and following delivery were 212 and 215 ng·ml−1, and occurred at 4.5 and 5 h, respectively. Mean plasma AUC values for proguanil during and following pregnancy were 94 and 98 ng·h·ml−1·kg−1, respectively. Corresponding whole blood AUC values were 361 and 396 ng·h·ml−1·kg−1. The mean elimination half lives and mean residence times of proguanil in plasma and whole blood were 12.3 and 19.6 h and 13.8 and 20.7 h respectively during pregnancy. Following pregnancy these values were 17.1 and 19.7 h for plasma and 19.7 h and 20.2 h for whole blood respectively. Mean peak plasma and whole blood concentrations of cycloguanil following pregnancy were 25 and 22 ng·ml−1 respectively. During pregnancy peak cycloguanil concentrations in both plasma and whole blood were markedly lower, 13 and 12 ng ml−1, respectively. Two pregnant women (neither of whom were restudied) were probably poor metabolisers of proguanil. The mean ratio of proguanil to cycloguanil plasma AUC was 16.7 in the third trimester of pregnancy and 7.8 following pregnancy, compared with less than 5 in previously reported studies. The concentrations of 4-chlorophenylbiguanide in both plasma and whole blood in pregnant subjects were also lower than those after pregnancy. These data show that blood concentrations of the active antimalarial metabolite cycloguanil are reduced in late pregnancy and that the currently recommended dose of proguanil could be inadequate for antimalarial prophylaxis in pregnant women.
    Materialart: Digitale Medien
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  • 48
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 265-269 
    ISSN: 1432-1041
    Schlagwort(e): Cyclosporine ; Renal transplantation ; pharmacokinetics ; intraindividual variation ; circadian variation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The intraindividual variability and circadian variation of oral cyclosporine (CsA) pharmacokinetics were studied over 24 h in 18 renal transplant recipients at steady state, and in 10 of the patients during a second 24 h period. The absolute percentage intraindividual difference in daytime AUC (0–12 h) ranged from 2% to 54% (mean 30%), and the corresponding variability in nighttime AUC (0–12 h) ranged from 5% to 80% (mean 34%). The pharmacokinetic variables t1/2, tmax and Cmax were more variable than the AUC (0–12 h) both during the day and at night. The evening trough level was significantly lower than the morning trough level; 185 ng · ml−1 versus 223 ng · ml−1. This, together with a significantly longer t1/2 in the night than the day, suggested circadian variability in the pharmacokinetics of CsA. In a separate retrospective study in 162 renal transplant recipients given CsA by constant intravenous infusion, repeated CsA blood concentration measurements at steady state showed lower concentrations during the day than the night, suggesting higher CsA clearance during daytime. It is concluded that CsA pharmacokinetics in renal transplant recipients, besides the well-known interindividual variability, also displays large intraindividual variability as well as circadian variation. Our findings further emphasize the necessity and difficulty of pharmacological monitoring in the clinical use of CsA in organ transplantation.
    Materialart: Digitale Medien
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 301-302 
    ISSN: 1432-1041
    Schlagwort(e): Adriamycin ; Haemodialysis ; adriamycinol ; pharmacokinetics ; moment analysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 305-306 
    ISSN: 1432-1041
    Schlagwort(e): Atenolol ; bioavailability ; intestinal absorption ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We investigated the dose proportionality after the intake of oral atenolol 25, 50, 100 and 150 mg. Standard tablets were taken by 8 healthy volunteers in randomised order of doses. The area under the curve divided by dose did not differ between the doses, indicating that the absorption of this hydrophilic compound, with known incomplete bioavailability, was constant over the range tested.
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 255-260 
    ISSN: 1432-1041
    Schlagwort(e): Ramipril ; Propranolol ; interaction ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the pharmacodynamic effects of ramipril, propranolol, and their combination, as well as the effect of propranolol on the pharmacokinetics of ramipril in 12 healthy men (age 24 (SD 6) y, weight 72 (7) kg). Propranolol and placebo, ramipril and placebo, or propranolol and ramipril were given orally for four days in a crossover, double-blind fashion. The pharmacokinetics of ramipril and ramiprilat were investigated on day 4. Effects on plasma renin activity, ACE activity, and heart rate and blood pressure both before and after a standardized exercise test were measured on days 1 and 4. On day 4 the combination reduced the mean arterial pressure by 2.8 mmHg compared with propranolol alone and by 3.7 mmHg compared with ramipril alone. Ramipril had no effect on the bradycardia induced by propranolol. Propranolol reduced exercise mean arterial pressure by 9 mmHg (day 4) and heart rate by 7 beats.min−1 (day 4) compared with ramipril; this was not affected by co-administration of ramipril. On day 4 the average plasma renin activity was not significantly higher than after the combination. ACE activity was not affected by propranolol. The pharmacokinetics of ramipril and ramiprilat were not influenced by propranolol. The combination of ramipril and propranolol has additive pharmacodynamic effects that may be useful in the treatment of hypertension.
    Materialart: Digitale Medien
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 275-277 
    ISSN: 1432-1041
    Schlagwort(e): Fenoterol ; Pregnancy ; pharmacokinetics ; premature labour
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of the β2-adrenergic drug fenoterol, which is used as a tocolytic agent in pregnancy, has been investigated in pregnant (n=9) and nonpregnant (n=5) women during a constant rate intravenous infusion. Clearance and mean residence time were found to be 1990 (1879/2220; Median, Q25/Q75) ml/min and 9.2 (8.0/14.0) min in the pregnant and 2126 (1915/2130) ml/min and 16.6 (16.5/32.1) min in the nonpregnant women, respectively. In addition, fenoterol clearance was estimated in 88 women from a single blood sample collected at steady state during IV therapy and the effect of gestational age on clearance was studied. Clearance displayed large inter-individual variation. There was no apparent correlation between clearance and gestational age. We conclude that there is no need to adjust the dose on pharmacokinetic grounds in the course of pregnancy.
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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 265-269 
    ISSN: 1432-1041
    Schlagwort(e): Brofaromine ; Debrisoquine oxidation ; MAO-A inhibitor ; polymorphism ; quinidine ; healthy volunteers ; cytochrome P450 ; drug metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The metabolic fate of brofaromine (CGP 11 305 A), a new, reversible, selective MAO-A inhibitor, has been assessed in poor (PM) and extensive (EM) metabolizers of debrisoquine. Compared to EM, PM had significantly longer t1/2 (136%) and larger AUC(0−∞) (110%) of the parent compound brofaromine and a lower Cmax (69%) and AUC (0–72 h) (40%) of its O-desmethyl metabolite. The mean metabolite/substrate ratio (based on urine excretion) was about 6-times greater in EM than in PM. Treatment with quinidine converted all EM into phenocopies of PM. All pharmacokinetic parameters of brofaromine and O-desmethyl-brofaromine in EM treated with quinidine were similar to those of untreated PM, including the metabolite/substrate ratio. Quinidine treatment of PM did not alter the pharmacokinetics of brofaromine or of its metabolite, nor the metabolite/substrate ratio. The results indicate a role for the debrisoquine type of oxidation polymorphism in the O-demethylation and pharmacokinetics of brofaromine.
    Materialart: Digitale Medien
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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 195-197 
    ISSN: 1432-1041
    Schlagwort(e): Cefotaxime ; Renal insufficiency ; desacetylcefotaxime ; pharmacokinetics ; children
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary It is generally assumed that the renal clearance of drugs in patients with renal impairment are affected to a similar extent regardless of the type of renal disease (intact nephron hypothesis). We have studied the effect of underlying renal disease on the pharmacokinetics of cefotaxime and desacetylcefotaxime in two groups of children (ages 7 to 16 y) with varying degrees of renal dysfunction. Patients in group 1 (n=5) had intrinsic renal disease and those in group 2 (n=5) had extrinsic renal disease, as identified by the primary renal lesion. After a single intravenous dose of cefotaxime timed blood and urine samples were collected for 24 h; cefotaxime and desacetylcefotaxime were measured by HPLC. There were no significant differences between the groups in age, body surface area, urine output, creatinine clearance, total body clearance, nonrenal clearance, renal clearance, and volume of distribution at steady state of cefotaxime, and renal clearance of desacetylcefotaxime. However, the renal clearance: creatinine clearance (CLR:CLCR) ratios for both cefotaxime [1.34 in group 1 vs. 0.51 in group 2] and desacetylcefotaxime [1.58 in group 1 vs. 0.75 in group 2] were statistically significant between the two groups. Group 1 patients had an average CLR:CLCR ratio greater than 1 for both the parent compound and the metabolite, suggesting that net tubular secretion was still intact, despite a diminished glomerular filtration rate (CLCR=24 ml·min−1·1.73 m−2). In contrast, patients in group 2 (CLCR=49) ml·min−1·1.73 m−2) had an average CLR:CLCR ratio less than 1 for both cefotaxime and desacetylcefotaxime, suggesting that renal tubular transport mechanisms did not remain functional in these patients. Our findings suggest that the effect of renal insufficiency on the renal elimination of cefotaxime and its metabolite desacetylcefotaxime may depend on the cause of renal insufficiency.
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  • 55
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 253-258 
    ISSN: 1432-1041
    Schlagwort(e): Bioelectrical impedance ; Gentamicin ; non-invasive technique ; neonates ; predictive models ; pharmacokinetics ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The use of bioelectrical impedance (BI) analysis as a non-invasive approach for individualising gentamicin therapy in newborn infants has been investigated in a two phase study. In Phase I, 1/impedance and length2 were identified as statistically significant predictors of the distribution volume of gentamicin (Adj R2=0.78, CV=12.42%), and length2/impedance and post-conceptual age were predictors of total systemic clearance (Adj R2=0.83, CV=14.5%), following the administration of 2.5 mg·kg−1 gentamicin to 17 neonates (gestational age (GA) 27 to 36 weeks). In a prospective validation of these relationships in an independent (Phase II) group of 27 infants (GA 26 to 41 weeks), predicted serum gentamicin concentrations were close to those achieved. Several instances of high prediction errors (predicted minus achieved levels) were observed in infants with known or suspected renal impairment and they caused significant (P〈0.05) perturbation in the bias and accuracy of the models. Daily BI measures over a four to five day period were able to detect individual changes in the fat-free body compartments, which were translated into alterations in gentamicin regimens. This simple, non-invasive and relatively inexpensive bedside technique provides a potentially valuable means to individualise gentamicin therapy without relying on the measurement of serum gentamicin concentration.
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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 313-320 
    ISSN: 1432-1041
    Schlagwort(e): Lorazepam ; CL284,846 ; Psychomotor performance ; memory function ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of single doses of CL284,846 (20 mg), lorazepam (2 mg) and placebo on psychomotor performance, memory function and subjective feelings were assessed in 12 normal, healthy male volunteers. Each subject received each treatment in balanced order and a minimum of 6 days was left between treatments. The subjects performance on a comprehensive battery of tests of psychomotor performance, memory function and subjective ratings was assessed pre-treatment and at 1, 3 and 5 h post-treatment. In general, the effects of CL284,846 on memory were similar to those of lorazepam at 1 h post-treatment but, recovery was rapid with CL284,846. Impairments induced by lorazepam persisted throughout the post-drug testing sessions. This pattern of effects was repeated across most of the variables tested. However, at 1 h, CL284,846 produced less marked psychomotor impairment than lorazepam. The results of this study suggest that CL284,846 is a safe, rapid acting and effective sedative with some clear advantages over lorazepam with respect to unwanted cognitive and psychomotor impairments.
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 357-360 
    ISSN: 1432-1041
    Schlagwort(e): Famotidine ; Reflux oesophagitis ; intraoesophageal long-term pH-metry ; pharmacodynamics ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics, pharmacodynamic effect and clinical efficacy of famotidine were studied in 10 patients with reflux oesophagitis Grades I and II. For the pharmacokinetic studies the patients received 20 mg famotidine i. v. The half-life of famotidine was 3.8 h, the total plasma clearance was 297 ml·min−1, and a steady state volume of distribution of 1.21·kg−1 was found. For pharmacodynamic assessment, intraoesophageal pH-metry was performed without and after acute treatment with famotidine 20 mg i. v. and following 3 weeks of oral famotidine 80 mg b. d. The resultant percentage total acid exposure time (pH〈4 within 24 h) were 23.9%, 19.0% and 19.2% (median), respectively (NS). At the end of 6 weeks of oral therapy, symptomatic and endoscopic improvement had occurred in 9 and 5 patients, respectively. Our study shows that the pharmacokinetics of famotidine in patients with reflux oesophagitis is comparable to that in healthy volunteers and peptic ulcer patients. The clinical response to the treatment appeared comparable to that found after other H2-receptor antagonists.
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  • 58
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 365-367 
    ISSN: 1432-1041
    Schlagwort(e): Ciprofloxacin ; Diazepam ; quinolone ; benzodiazepine ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of pretreatment with a seven day course of ciprofloxacin on pharmacokinetics and pharmacodynamics of an intravenous (5 mg) dose of diazepam were investigated in a group of 12 healthy volunteers in a double-blind placebo-controlled crossover study. Ciprofloxacin pretreatment significantly reduced diazepam CL (without ciprofloxacin: 19.5 ml·h−1kg−1; with ciprofloxacin: 12.3 ml·h−1kg−1). Diazepam t1/2 was also prolonged (without ciprofloxacin: 36.7 h; with ciprofloxacin: 71.1 h), but volume of distribution was unaltered (without ciprofloxacin: 1.1 l·kg−1; with ciprofloxacin: 1.1 l·kg−1). However, no significant changes were detected in psychometric tests of digit symbol substitution, tapping rate and short memory, as well as levels of concentration, vigilance and tension measured by visual analogue scales.
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  • 59
    ISSN: 1432-1041
    Schlagwort(e): Temocapril ; Liver dysfunction ; angiotensin converting enzyme inhibitor ; diacid ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Six subjects with normal liver function (Group 1) and 7 patients with liver dysfunction (Group 2; mean ICGR15 value 30.5 (5.2) %; range 16 to 56) received a single oral dose of 1 mg temocapril, a prodrug-type ACE inhibitor, with preferentially excreted by the biliary route. The plasma temocapril concentrations in Group 2 at 30 min and 1 h postdose were significantly higher than in Group 1, but the difference had disappeared 2 h postdosing. Although the half life of temocapril diacid in Group 2 was significantly longer than in Group 1, there was no significant difference between the two groups in AUC, Cmax or tmax. In Group 2, urinary recovery of temocapril was significantly increased, suggesting a possible delay in the bioactivation of temocapril into the diacid, but recovery of the diacid itself was not abnormal. ACE inhibitory action in Group 2 remained unchanged. Temocapril is regarded as an ACE inhibitor the disposition and efficacy of which are little affected in patients with impaired liver function.
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  • 60
    ISSN: 1432-1041
    Schlagwort(e): Isradipine ; Diclofenac ; pharmacokinetics ; platelet aggregation ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In this open, two-period crossover study in 18 healthy male volunteers, a single oral dose of 50 mg diclofenac was administered alone and on day 7 of multiple oral dosing of 5 mg b.i.d. isradipine to assess a possible pharmacokinetic interaction. The effect of these drugs on ex vivo platelet function was also determined. Serial blood samples were obtained over 12-hour periods on three occasions: after the single diclofenac dose; after the morning dose of isradipine on day 6 and after co-administration of both drugs on day 7 of steady-state isradipine administration. Additional samples were taken at 2 h post dose for determination of ex vivo platelet aggregation. Isradipine plasma concentrations were determined by a gas chromatographic method and diclofenac plasma concentrations by an HPLC method. The pharmacokinetic characteristics of diclofenac were unaltered during co-administration. The maximum plasma concentration of isradipine was increased 19.6% during co-administration from 5.06 to 6.05 ng·ml−1. This is not expected to be of clinical importance. Isradipine's apparent total body clearance and steady-state AUC remained unchanged. Ex vivo induced platelet aggregation was not affected by any of the treatments.
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 555-558 
    ISSN: 1432-1041
    Schlagwort(e): Glucagon ; pharmacokinetics ; i.v. infusion ; intranasal spray ; intramuscular administration ; insulin-dependent diabetes mellitus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of intranasal, an intravenous infusion, and intramuscular glucagon has been studied in 5 healthy subjects and 11 patients with insulin-dependent diabetes mellitus. After infusion the elimination half-life was significantly longer in diabetics (11.9 vs 6.6 min) and the apparent volume of distribution was twice as high in diabetics (0.19 vs 0.37 l·kg−1). The metabolic clearance rates were the same in the two groups (18.9 and 21.3 ml·min−1·kg−1 in controls and in diabetics) and were about twice those previously reported. After 1 mg intranasally the Cmax of immunoractive glucagon (IRG) was similar in diabetic and in healthy subjects. Administration of a higher dose (2 mg) to diabetic patients produced a higher plasma level, although not proportionately so. The AUC after 1 mg was also similar in controls and in diabetics. The elimination half-life in both groups was similar to the value found after IV infusion; it was significantly shorter in controls (5.5 min) than in diabetics (13.8 min). In both groups, mean Cmax was significantly lower than after IM glucagon, the relative bioavailability of 1 mg intranasally vs IM injection being less than 30%. After IM administration, the Cmax and AUC of IRG in controls and in diabetic patients, were identical. The apparent elimination half-life was also similar in the two groups, and was three- to four-times longer (28.6 and 31.4 min) than after infusion or intranasal administration, possibly because estimation of the t1/2 was affected by slow release of the hormone from the site of injection.
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  • 62
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 563-569 
    ISSN: 1432-1041
    Schlagwort(e): Chlorpromazine ; metabolites ; N-oxide ; sulfoxide ; 7-hydroxy ; conjugates ; pharmacokinetics ; first pass metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A study was carried out in 11 healthy young men to investigate the pharmacokinetics of chlorpromazine (CPZ) after a bolus intravenous (IV) dose (10 mg) and three single oral doses (25, 50 and 100 mg), with a washout period of two weeks between doses. Plasma levels of CPZ, CPZ N-oxide (CPZNO), CPZ sulfoxide (CPZSO) and both free and conjugated 7-hydroxy-CPZ (7-HOCPZ) were measured by extraction radioimmunoassays. CPZ exhibited multicompartmental pharmacokinetics in most subjects. There was wide between-subject variability in half life (11.05 h), volume of distribution (1215 l), volume of distribution at steady state (642 l) and mean residence time (8.88 h), whereas systemic clearance was somewhat less variable (76.6 l·h−1). All metabolites were present in measurable concentrations in the plasma of 9 of 11 subjects after IV CPZ, whereas free 7-HOCPZ was not detected in the other 2 individuals. With the exception of CPZNO, the biological half lives of the primary metabolites were longer than the half life of CPZ. After oral administration, the percentage of CPZ reaching the systemic circulation intact (F%) was very low (4–38%) and dose dependant. Moreover, both within-subject and between-subject variances were very high. The maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve extrapolated to infinite time (AUC) showed evidence of nonlinearity, whereas half life did not appear to be dose dependant. These data suggest that the high degree of variability in the pharmacokinetics of CPZ is a result of extensive first pass metabolism rather than variation in half life. The mean AUC for the total conjugates of 7-HOCPZ was about two fold higher than that of the parent drug or any other metabolite. This shows that phase II metabolism plays a very significant role in the disposition of CPZ. As a result, the role of CYP2D6 in the 7-hydroxylation of CPZ cannot be fully assessed without taking phase II metabolism into account.
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 585-587 
    ISSN: 1432-1041
    Schlagwort(e): Flumazenil ; benzodiazepine ; absorption ; disposition ; elderly volunteers ; pharmacokinetics ; aging
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In an open design, randomised, two-way cross-over study, a single 2 mg i.v. dose and a single 30 mg oral dose of flumazenil were each administered to a group of healthy young (n=6) and elderly (n=12) volunteers (male: female 2/1). Plasma samples were collected at intervals and intact drug was assayed. Both the IV and oral doses of flumazenil were very well tolerated by both age groups and no severe or unexpected adverse effects were observed. The main complaints were dizziness and headache, mainly after oral dosing, probably due to the higher Cmax and AUC following this route of administration. After 2 mg i. v. the disposition parameters in the two age groups (elderly/young) were very similar: volume of distribution (Vss): 0.88/0.901·kg−1; total body clearance (ClPL): 0.86/0.99 l·min−1; terminal elimination half-life (t1/2β): 1.02/0.91 h. After the 30 mg oral dose the mean Cmax of 87.6 ng·ml−1 (elderly) and 78.4 ng·ml−1 (young) were generally reached within 0.5 to 1 h. In 26% (elderly) and 23% (young), the absolute bioavailability of flumazenil was very similar. It is concluded that the absorption and disposition paramters of flumazenil were not significantly affected by aging.
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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 27-33 
    ISSN: 1432-1041
    Schlagwort(e): Nicorandil ; vasodilator ; tolerance study ; blood pressure ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the effects of intravenous nicorandil, a mixed arterial and venous vasodilator, in 48 healthy volunteers. Nicorandil (20, 28, 39, 54, 74, 103, 144, or 200 μg·kg−1) or placebo were given over 5 min to subjects supine (16 subjects, 2 doses) or sitting (32 subjects, 1 dose) in a single-blind crossover design. Electro-cardiographic intervals, blood pressure, and heart rate were measured before and for 8 h after dosing. Blood and urine safety laboratory studies were also performed before and after dosing. All intravenous infusions of nicorandil and placebo were well tolerated and there were no clinically important safety concerns. The most frequent adverse event after nicorandil was headache (24 events by 19 subjects), although its occurrence was not strictly dose related. One subject experienced transient symptomatic hypotension (144 μg·kg−1). Mean plasma nicorandil concentrations were dose-related and fell with a half-life of 0.7 to 1.2 h. Systemic clearance and volume of distribution tended to decrease as dose increased. Sitting subjects showed marginally lower (〈20%) systemic clearances and larger values of Cmax and AUC. Nicorandil produced dose-related reductions in blood pressure, with consistent statistically significant differences from placebo after the 144 and 200 μg·kg−1 doses. The falls in blood pressure were greater for diastolic pressure and in this supine position. At 200 μg·kg−1, the mean falls in systolic/diastolic pressures (mm Hg) during the first hour were 10.9/14.7 supine and 6.1/9.1 sitting; systolic pressure returned to baseline after 8 h and diastolic pressure after 4 h. Heart rate increased transiently (mean peak increase of 17–24 bpm at the end of the 144 and 200 μg·kg−1 infusions). Blood pressure and heart rate changes over time were statistically significantly correlated with plasma nicorandil concentrations. Individual areas under the blood pressure and heart rate change curves likewise correlated with plasma concentration curve areas.
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  • 65
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. S31 
    ISSN: 1432-1041
    Schlagwort(e): Cefmenoxime ; Renal failure ; continuous haemofiltration ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The elimination of cefmenoxime after single and repeated i. v. dosing was studied in 12 patients with severe renal failure and sepsis during continuous haemofiltration. More than 30 % of the drug was found in the filtrate. The sieving coefficient (S) was 0.54. Vss % was unchanged 0.311 · kg−1 in comparison with patients with normal renal function, whereas the mean t/12ß was prolonged to about 16 h, and total clearance was reduced 20.8 ml · min−1 · 1.73 m−2. Once daily administration of 1 g cefmenoxime is suggested as the appropriate dose under such circumstances.
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 171-176 
    ISSN: 1432-1041
    Schlagwort(e): Oxprenolol ; β-adrenoceptor blockade ; circadian rhythm ; haemodynamics ; pharmacokinetics ; exercise ; healthy volunteers ; kinetic-dynamic model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the effect of dosage time of oxprenolol (Trasicor®) on its pharmacokinetics and pharmacodynamics in six healthy volunteers. The drug effects measured were heart rate and systolic blood pressure during exercise. Oxprenolol was taken orally at 08.00 h, 14.00 h, 20.00 h, and 02.00 h in randomized order, with 1 week between successive doses. There were differences in the pharmacokinetics of oxprenolol for the ratio between the apparent volume of distribution and systemic availability (P=0.04) and for elimination half-life (P=0.006). Both were lowest after administration at 14.00 h (163 (77) l and 1.2 (0.6) h; mean (SD)) and highest after administration at 02.00 h (229 (100) l, and 1.7 (0.6) h). The systolic blood pressure during exercise before oxprenolol did not vary with dosage time, but heart rate during exercise before intake was lowest before dosage time 08.00 h and highest before dosage time 20.00 h (P=0.03). The time-course of heart rate during exercise after oxprenolol was described by a model that incorporated the factors drug concentration and spontaneous diurnal variation. EC50 and Emax did not vary between dosage times. The spontaneous diurnal variation in heart rate during exercise was unaffected by oxprenolol, leading to an apparently greater effect of oxprenolol during the night than during the day.
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  • 67
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. S53 
    ISSN: 1432-1041
    Schlagwort(e): Quinapril ; Renal failure ; quinaprilat ; haemodialysis ; ACE inhibitor ; pharmacokinetics ; pharmacodynamics ; peritoneal dialysis ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and pharmacodynamics of the ACE inhibitor quinaprilat have been studied in six chronic haemodialysis (HD) patients and in six patients undergoing continuous ambulatory peritoneal dialysis (CAPD) after a single oral dose of 2.5 mg quinapril. Mean tmax and Cmax values (SEM) for quinaprilat in interdialytic HD patients were 4.0 (0) h and 84 (8.4) ng · ml−1 respectively, and they did not differ significantly from those in CAPD patients (4.7 (0.7) h and 64 (5.7) ng · ml−1). Elimination half lives were 30 (10.1) h (HD) and 34 (7.3) h (CAPD). Cmax, tmax, t/12, and AUC were increased and CL was decreased compared to data reported previously after giving 2.5 mg to healthy subjects. Peritoneal clearance was calculated as 0.1 (0.1) ml · min−1, thus less than 0.5 % of the dose were removed within 24 h by CAPD. ACE activity was suppressed by more than 93 % between 4 and 24 h postdose (P 〈 0.001). It decreased in both groups with increasing plasma quinaprilat levels. Angiotensin II concentration compared to baseline was significantly decreased at 4 hours (−30.4±10 %) and 24 h (−30±9.9 %) (P 〈 0.05,n=11), while active plasma renin concentration was still significantly increased at 48 h postdose (+60.2±14.5 %,P 〈 0.01). Mean arterial pressure 24 h postdose was significantly (P 〈 0.05) decreased in HD (−12 mm Hg) and CAPD patients (− 20 mm Hg). Only two patients reported unwanted effects (fatigue, dizziness, nausea, and weakness). In conclusion, due to its long lasting effect on ACE activity and on blood pressure in terminal renal failure a starting dose of quinapril 2.5 mg o. d. may be used in hypertensive HD and CAPD patients.
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 361-364 
    ISSN: 1432-1041
    Schlagwort(e): Tulobuterol ; β2-adrenoceptor agonist ; aerosol inhalation ; transdermal delivery ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the pharmacokinetics of tulobuterol given transdermally or by aerosol inhalation in healthy male volunteers. Tulobuterol was rapidly absorbed after inhalation, with a tmax of 0.8–1.5 h. The Cmax and the AUC increased linearly with dose. Tulobuterol was well absorbed after transdermal administration, with an absorption lag-time of about 4 h. The Cmax and AUC increased linearly with dose and the tmax was about 9–12 h. The mean percentage of drug absorbed during the application of a patch for 24 h was 82–90% after a single dose and 82–85% during repeated dosing. The mean urinary recoveries as unchanged drug after a single inhalation and patch application were 3–4% and 5–6% respectively. Tulobuterol did not accumulate during repeated inhalation or transdermal application. It was well tolerated, except for an increase in heart rate of 10–20 beats · min−1 after five repeated applications of a 4 mg patch.
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 387-389 
    ISSN: 1432-1041
    Schlagwort(e): Flosequinan ; Congestive heart failure ; elderly ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have investigated the pharmacokinetics of the direct vasodilator flosequinan in elderly patients with congestive heart failure. Eight patients received a single dose of 50 mg, and 8 patients received once-daily treatment with 25 mg for two weeks. In the single dose study, the tmax of flosequinan was 2.5 h, Cmax was 1.17 μg · ml−1 and t1/2 was 5.63 h. The tmax of the metabolite BTS 53554 was 20.3 h, Cmax was 1.44 μg · ml−1 and t1/2 was 62.0 h. BTS 53554 accumulated gradually in the 14-day repeated dose study and steady-state was reached after approximately 2 weeks. Flosequinan was not found to accumulate. Adverse reactions were not observed in either the single or repeated dose study. It is advisable to consider renal function and body weight when flosequinan is to be administered to elderly patients with congestive heart failure. The initial dose should be 25 mg.
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  • 70
    ISSN: 1432-1041
    Schlagwort(e): Metoprolol ; controlled-release formulation ; hydrochlorothiazide ; pharmacokinetics ; pharmacodynamics ; healthy volunteers ; efficacy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied a controlled-release formulation containing metoprolol 100 mg and hydrochlorothiazide 12.5 mg. We compared the pharmacokinetics of both substances and the pharmacodynamics of metoprolol with those of a conventional combination tablet. The controlled-release formulation gave less variable plasma metoprolol concentrations, Cmax 138 nmol·l−1 and Cmin 74 nmol·l−1, whereas for the conventional formulation the mean Cmax of metoprolol was 629 nmol·l−1 and the Cmin 20 nmol·l−1. Despite lower relative systemic availability (68%) for metoprolol from the controlled-release formulation and a smaller AUC, metoprolol from the controlled-release formulation produced a greater total effect, calculated as the area under the curve of the effect on exercise heart rate vs. time (303 vs. 259%·h; P〈0.05). Hydrochlorothiazide was rapidly absorbed from both formulations and the plasma concentration profiles were almost superimposable. Controlled-release metoprolol with hydrochlorothiazide combines effective β1-adrenoceptor blockade for 24 h without affecting the pharmacokinetics of hydrochlorothiazide.
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  • 71
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 195-196 
    ISSN: 1432-1041
    Schlagwort(e): Digoxin ; Amiloride ; Canrenoate ; inotropism ; healthy volunteers ; potassium sparing diuretics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
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  • 72
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 287-291 
    ISSN: 1432-1041
    Schlagwort(e): tolmesoxide ; hypertension ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Tolmesoxide is a new, direct-acting vasodilator drug for use in the management of both hypertension and cardiac failure. In 6 essential hypertensives inadequately controlled by combined β-blocker and diuretic therapy (average supine blood pressure 178/103 mm Hg) the addition of tolmesoxide (300–900 mg daily) was associated with a significant improvement in blood pressure control (average supine blood pressure 161/89 mmHg). The effect of food on the pharmacokinetics and pharmacodynamics of tolmesoxide have also been studied because, particularly at higher doses, the drug has been associated with upper gastrointestinal upset and it has been empirically recommended that it be taken with food. The blood pressure and heart rate responses were not significantly different when tolmesoxide was taken fasting or with food. Food resulted in a significant reduction in the peak plasma tolmesoxide concentration (2.14 µg/ml compared to 2.97 µg/ml) and a significant increase in the time to reach peak plasma concentration (1.67 h compared to 0.63 h). Although there was no impairment of its hypotensive effect, food significantly altered the pharmacokinetics of tolmesoxide and may therefore be useful in reducing the gastrointestinal disturbance associated with its use. In the treatment of inadequately controlled hypertension, tolmesoxide has a limited role as an alternative vasodilator.
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  • 73
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 307-310 
    ISSN: 1432-1041
    Schlagwort(e): piretanide ; renal failure ; high dose ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of piretanide was studied in patients with renal failure. After oral administration of a high dose of piretanide (96 mg), the pharmacokinetic parameters were: elimination rate constant 0.346±0.072 h−1, half life 2.00±0.35 h, and total plasma clearance 119.55±35.90 ml · min−1. Compared to the values obtained in adults with normal renal function, these results show a decrease in total plasma clearance, but conservation of the metabolic clearance which amounts to 45% of the total clearance in the healthy adult.
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  • 74
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 397-402 
    ISSN: 1432-1041
    Schlagwort(e): ergotamine ; migraine ; radioimmunoassay ; clinical effects ; adverse effects ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The systemic availability of ergotamine after a single therapeutic oral or rectal dose was studied using a radioimmunoassay during the headachefree state in 24 patients suffering from migraine. Plasma concentrations of the drug were compared with anamnestic data about its clinical effects in the same patients. Among 12 patients with a good therapeutic response to medication, the mean plasma ergotamine levels stayed in the range 0.20 to 0.50 ng/ml for 6h. Their mean plasma levels at 30 min (0.33ng/ml) and 1h (0.40ng/ml) were significantly higher than those (0.06 and 0.08ng/ml, respectively) in 9 patients with only a moderate therapeutic response. In 9 patients with a moderate and 3 with a poor therapeutic response, the mean plasma level generally stayed below 0.10ng/ml. The mean peak concentrations in moderate (0.13 ng/ml) and poor (0.11ng/ml) responders appeared later (at 3h) than in good responders (at 1h). Side effects of the medication appeared to be associated with relatively low plasma levels of ergotamine and also with delayed maximum plasma concentrations of the drug. The present results suggest that the time of the maximum plasma drug level is an important determinant of the clinical effects of ergotamine, and that a good therapeutic response may be expected if a plasma ergotamine level of 0.20ng/ml or more is achieved within 1 hour after oral or rectal administration.
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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 343-350 
    ISSN: 1432-1041
    Schlagwort(e): orphenadrine ; single dose ; multiple doses ; bioavailability ; pharmacokinetics ; N-demethylorphenadrine ; metabolism ; dog ; man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentrations of orphenadrine were measured by a specific gaschromatographic method in 5 healthy male volunteers after a single oral dose of orphenadrine hydrochloride 100mg. The single dose pharmacokinetic profile of orphenadrine was evaluated from these data. The elimination half-life ranged from 13.2–20.1 h after the commercial tablet formulation. Plasma concentrations, determined in volunteers and patients under different conditions of repeated oral administration of the same formulation of orphenadrine hydrochloride exceeded the theoretical values, predicted from the single dose pharmacokinetics, by a factor 2 to 3. The elimination half-lives after discontinuation of treatment showed a 2 to 3-fold increase over the single dose values. This demonstrates a clear discrepancy between the multiple and single dose pharmacokinetics of orphenadrine. Experiments in dogs suggested competition for biotransformation between orphenadrine and its metabolite N-demethylorphenadrine. Product inhibition of this type could explain the observed discrepancy.
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  • 76
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 273-279 
    ISSN: 1432-1041
    Schlagwort(e): amoxycillin ; i.v. administration ; pharmacokinetics ; two- and three-compartment models
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic characteristics of amoxycillin were studied in healthy volunteers after intravenous injection of 250 mg, 500 mg and 1,000 mg, and infusion of 2 g and 5 g. Serum concentrations were fitted using either bi- and tri- exponentional equations. Comparison of the regression curves obtained revealed that the three-compartment model gave a better fit to the serum concentration versus time curve. It was evident that there was a third, slow, dose dependent phase of disposition. This result has been confirmed by the fact that the terminal half life of amoxycillin on cessation of a continuous infusion is significantly greater than after acute administration.
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  • 77
    ISSN: 1432-1041
    Schlagwort(e): indapamide ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Two formulations of indapamide tablets (2.5 mg) were given as a 5.0 mg dose and the subsequent blood levels were compared to those obtained after administration of a 5.0 mg solution. The study was conducted as a randomized three-way crossover design using healthy male volunteers. The drug was well tolerated by all the subjects involved. The area under the blood concentration versus time curve, extrapolated to infinity was essentially the same for all three formulations (4.2, 4.7, and 4.4 µg-h/ml). Statistical comparison of the blood levels from the two tablets showed that one tablet had a significantly greater maximum blood concentration (263 vs 231 ng/ml) and a significantly shorter time of maximum blood concentration (2.3 vs 3.5 h). Cmax (333 ng/ml) and tmax (0.7 h) values for the solution were significantly higher than either tablet. The average half-life (β-phase) for all three formulations was 15 h, while the average systemic clearance was 20 ml/min. Indapamide has a low clearance rate and there was no evidence that the drug undergoes a first-pass effect.
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 257-264 
    ISSN: 1432-1041
    Schlagwort(e): TRIS buffer ; metabolic acidosis ; pharmacokinetics ; cellular uptake ; renal excretion ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To investigate the pharmacokinetics of TRIS, an infusion of the buffer was given to 6 healthy volunteers (121 mg/kg=1 mmol/kg; pH 7.4) and to 20 patients suffering from metabolic acidosis (109–376 mg/kg; pH 10.9). The drug exhibited two-compartment characteristics in volunteers (t0.5,β=5.6 h) and patients with intact renal function (t0.5,β=16.3–45.6 h). The final volume of distribution (Vβ) indicated uptake into tissues, but equilibration between body compartments was slow. Mainly unchanged TRIS was eliminated by the kidney; 82% of the administered dose was recovered from 24 h-urine of healthy subjects. In the patients a linear correlation between creatinine-clearance and TRIS-clearance was observed, the latter always being somewhat greater than the former. Only insignificant amounts of the drug were found in bile and gastric juice. In anuric patients the plasma concentration of TRIS declined monoexponentially, with a half-life between 10 and 58 h. Haemodialysis or haemofiltration did not influence this process. From the data it seems questionable whether cellular uptake of TRIS is an important factor in the therapy of intracellular acidosis, but the possibility of drug accumulation must be borne in mind if repeated doses are given to the same patient.
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  • 79
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 301-308 
    ISSN: 1432-1041
    Schlagwort(e): tranylcypromine ; tryptamine excretion ; monoamine oxidase inhibition ; norepinephrine pressor test ; tyramine pressor test ; pharmacodynamic half-life ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The inhibition of monoamine oxidase (MAO) by tranylcypromine was studied in 6 healthy volunteers given increasing doses of 10, 15, 20 and 25 mg/day over a 4 week period. Measurements were made of urinary tryptamine excretion, blood pressure response to tyramine (TY) and norepinephrine (NE), and subjective self-rating. A significant increase in urinary tryptamine, indicating the onset of MAO inhibition, occurred in all 6 subjects once the cumulative dose of 40 mg TC had been administered. Thereafter, urinary tryptamine increased up to 7-fold, dose-dependently with large interindividual variation (78±27 to 549±252 µg/g creatinine). Within 4 days after stopping the drug, control values were reached again. The assessment of TY potentiation by comparison of equieffective doses (Sdose) became up to 10 times more sensitive when both the height and the duration of the increase in systolic blood pressure (SAUC) were taken into account. The increases in tyramine sensitivity found with the highest cumulative doses of TC (5.4±0.8 mg/kg; n=6) were Sdose from 8–16 and SAUC from 28–162, respectively. The pharmacodynamic half-life (Pd1/2) of TC approximated a mean first fast Pd1/2 of 1.3 d and a slower phase of 14.2 d. During treatment with the highest TC dose, resting blood pressure was significantly elevated from 120 to 128 mm Hg, and the pressor sensitivity to NE (SNE) in 4 of the 6 subjects rose, the mean was 1.7 (n=6). In 3 volunteers NE sensitivity was normalized within 4 days after stopping TC. There was a significant correlation between increasing vigilance with TC dose in 5 volunteers (r=0.81, n=15, p〈0.01). It is concluded that combination of the results of several tests has provided reliable information about the onset, extent and duration of MAO inhibition in healthy volunteers.
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  • 80
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 75-80 
    ISSN: 1432-1041
    Schlagwort(e): psoriasis ; 8-methoxypsoralen ; food influence ; suction blister fluid ; serum ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of food on the kinetics of 8-methoxypsoralen (8-MOP) in serum and suction blister fluid was evaluated in a cross-over study in 19 psoriatic patients under PUVA treatment. The peak serum concentration of 8-MOP was reached 1.5 h after ingestion on an empty stomach, and in suction blister fluid the maximum concentration was already present in the first sample taken after 2 h, the time when UVA radiation was given. The postprandial kinetics of 8-MOP in serum and suction blister fluid differed, the highest levels being reached, respectively, at 2.4 and 3 h after intake, i.e. in both body fluids after irradiation had started. The side effects of 8-MOP, such as nausea and dizziness, in the two groups were similar. The present results indicate that to optimize the therapeutic effect of PUVA in individual patients, 8-MOP should be given on an empty stomach.
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  • 81
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 189-195 
    ISSN: 1432-1041
    Schlagwort(e): befunolol ; propranolol ; pharmacokinetics ; pharmacodynamic effects ; beta-adrenoceptor blocking agent
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Repeated doses of a new β-adrenoceptor blocking agent, befunolol, were administered orally to adult male volunteers for a cross-over comparison with propranolol. The β-adrenoceptor blocking activity of befunolol was greater than that of propranolol when assessed by the percentage reduction in exercise-induced tachycardia. The elimination half-life of drug was significantly prolonged on repeated administration of propranolol, but not of befunolol. The percentage reduction in exercise-induced tachycardia was highly correlated with the log plasma level of each drug. Both drugs produced a significant reduction in pre-exercise systolic and diastolic blood pressure, and significant attenuation of exercise-induced rise in systolic blood pressure.
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  • 82
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 235-240 
    ISSN: 1432-1041
    Schlagwort(e): ergotamine ; pharmacokinetics ; migraine ; plasma drug levels ; i.v. administration ; i.m. administration ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of ergotamine has been investigated in migrainous patients using a new, specific, sensitive HPLC assay (detection limit 100 pg/ml plasma). 10 patients were given ergotamine tartrate 0.5 mg i.v. and 5 of them received the same dose i.m. 2–3 weeks later. Blood samples were collected for up to 54 h following administration and the plasma concentration were analysed. After intravenous administration the plasma ergotamine declined rapidly, with an initial distribution half-life of 3 min followed by a mean terminal half-life of 1.86 h (range 90–155 min). The mean total plasma clearance was 11.0 ml kg−1 min−1, and the volume of distribution (Vdβ ) was 1847.6 ml kg−1. Individual t1/2β showed a positive linear correlation with the individual Vdβ . The intramuscular absorption of ergotamine was rapid and maximum plasma levels were usually obtained 10 min following administration. The biological availability was incomplete and variable at 46.6% (range 28.3–60.8%).
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  • 83
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 327-330 
    ISSN: 1432-1041
    Schlagwort(e): bendroflumethiazide ; cantharides plasters ; blister fluid ; plasma levels ; pharmacokinetics ; compartmental analysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of bendroflumethiazide (BFT) was investigated following the oral administration of 10 mg to 3 healthy volunteers. Each subject participated twice in the study. BFT was determined in plasma and cantharides blister fluid from 1/2 to 30 h post administration. Blister fluid was obtained from blisters 10–22 h old. Plasma levels were fitted to a tri-exponential equation and the concentration of the drug in the peripheral compartment was calculated from the microscopic rate constants. In 5 of 6 cases investigated, cantharides blister fluid levels paralleled the concentration of the drug in the peripheral compartment. The mean blister fluid levels exceeded the calculated concentration in Compartment 2 1.46 fold. In one case, the blister fluid level paralleled the plasma level. This subject clearly differed from the others as more than 10 h were required for blister formation in her. The results suggest that following the administration of BFT, cantharides blister fluid behaves as part of the peripheral compartment. The possible value of studying blister fluid levels in pharmacokinetic investigations is discussed.
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  • 84
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 343-347 
    ISSN: 1432-1041
    Schlagwort(e): valproic acid ; fatty acids ; plasma protein binding ; pharmacokinetics ; drug metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of physiologic variations of free fatty acid levels on in vivo valproic acid plasma protein binding was studied in 6 healthy adult subjects. 14 blood samples were taken during a 12-h dosing interval at steady state while in a fed condition and also during a 27 h fast. Free fraction and total valproate concentration were determined by equilibrium dialysis and GLC, respectively. Free fatty acid levels were determined from both fresh samples and samples incubated at 37°C for 12 h, the latter in order to simulate equilibrium dialysis conditions. Fasting resulted in increased serum free fatty acid levels in all subjects, ranging from 34–182% (p〈0.01). Incubation also caused free fatty acid levels to rise, more so in fed samples (50–87%,p〈0.01) than in fasting samples (10–50%,p〈0.01). Fasting resulted in a 9% increase in the mean free fraction for all subjects combined (p〈0.01). Regression analysis of 180 sets of values for free fraction, total valproate concentration and free fatty acid level suggested that valproate concentration accounts for 17% and free fatty acid level for 37% of the variation in free fraction. Mean clearance was unchanged by fasting despite an increased free fraction suggesting decreased intrinsic clearance (i.e. decreased metabolism) of valproate under these conditions.
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  • 85
    ISSN: 1432-1041
    Schlagwort(e): L-threo-3,4-dihydroxyphenylserine ; familial amyloid polyneuropathy ; pharmacokinetics ; norepinephrine ; pressor response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of oralL-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was studied in 7 normal subjects and 7 patients with familial amyloid polyneuropathy. Each person swallowed a single 300 mg dose in the fasting state, andL-threo-DOPS in plasma and urine was determined by high performance liquid chromatography with an electrochemical detector after separation on a boric acid gel column.L-threo-DOPS was slowly absorbed by normal subjects; the maximum plasma concentration occurred 3 h after administration and 20% of the oral dose was recovered unchanged in the urine within 12 h. It induced a substantial elevation of plasma norepinephrine levels, the peak being attained at 5 h, but without any change in blood pressure. In the patients, the absorption and metabolism ofL-threo-DOPS were delayed, and a prolonged pressor response was observed, with a peak after 8 h. It was concluded that the effects on plasma norepinephrine and blood pressure of oralL-threo-DOPS were essentially equal to those of twice as large a dose ofDl-threo-DOPS.
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  • 86
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 501-504 
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; uraemia ; dosing regimen ; prediction ; computer program ; old age ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Using a recently developed computer program based on a correlation between methods to predict the elimination half-life and apparent volume of distribution of cimetidine and actual data from patients, ideal dosage regimens were generated for patients with renal impairment and for geriatric patients, together with the corresponding maximum and minimum steady state concentrations. Using the ideal dosage regimens, practical regimens with feasible dosing intervals of 6, 8 and 12 h were computed, which should result in therapeutic concentrations of 0.4 to 1.3 µg/ml. For uraemic patients and geriatric patients above the age of 75 years it would be desirable to have an additional oral 100 mg dosage form.
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  • 87
    ISSN: 1432-1041
    Schlagwort(e): amitriptyline ; imipramine ; clomipramine ; antidepressant overdose ; clinical effects ; pharmacokinetics ; cardiotoxicity ; maprotiline ; doxepine ; nortriptyline ; opipramol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24 h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 µg/l, with concentrations above 500 µg/l in 11 cases. The serum amitriptyline concentration remained high for 3–4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 µg/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidpressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60–500 µg/l) but not high (〉500 µg/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
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  • 88
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 1-5 
    ISSN: 1432-1041
    Schlagwort(e): clonidine ; noradrenaline ; pharmacokinetics ; arterial blood pressure ; plasma concentration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of clonidine and its relation to blood pressure response and side effects were studied after single oral doses of 75 µg, 150 µg and 250 µg in normotensive subjects. Following oral administration, the drug was absorbed rapidly after an initial lag time of 19–22 min and peak levels were reached between 2.4 and 2.9 h. Sampling over 48 h was necessary for accurate estimation of pharmacokinetic parameters. Post-peak plasma concentration declined in a monoexponential manner and the half-life of the elimination phase ranged from 9.0 to 15.1 h. Maximum plasma concentration (Cmax) and area under curve (AUC) increased proportionally with increasing doses. Clonidine produced significant reductions in the pulse rate and a dose dependent decrease in blood pressure. Clonidine (150 µg) also produced significant reductions in plasma catecholamine levels.
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  • 89
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 43-47 
    ISSN: 1432-1041
    Schlagwort(e): timolol ; pharmacokinetics ; pharmacodynamics ; healthy subjects ; cardiac infarction patients ; i.v. therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Disappearance pharmacokinetics, pharmacodynamics and general tolerance of i.v. timolol were compared in 12 healthy volunteers and 10 patients with a definite or proven acute myocardial infarction. The drug was administered to the patients immediately on arrival at the hospital after a median delay time of 4 h. Tolerance to the injections was good in both volunteers and patients. The study revealed disappearance pharmacokinetics that were similar in volunteers and patients.
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  • 90
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 293-301 
    ISSN: 1432-1041
    Schlagwort(e): metipranolol ; deacetyl metipranolol ; pharmacokinetics ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic parameters of deacetyl metipranolol were determined after i.v. infusion of increasing doses (6–25 mg) in 17 normal volunteers. In a second cross-over trial, deacetyl metipranolol 10 and 20 mg were infused in a further 10 subjects, and in a third trial another 20 volunteers received metipranolol 40 mg orally. Metipranolol is very rapidly and completely deacetylated in man, so all pharmacokinetic data refer to deacetyl metipranolol, which was assayed by gas chromatography-mass spectrometry. The pharmacokinetic analysis was performed using a recently developed model, using a volume of distribution which is variable with time. The following data were obtained after oral administration: (mean values); lag-time 7.3 min; tmax 50 min, invasion half-life 6.3 min; elimination half-life 3 h; urinary excretion of unchanged drug approximately 4% of the dose. The experiments with infusion of increasing doses, as well as the cross-over study with 10 and 20 mg i.v., showed dose-linearity of the kinetics. The respective mean half-lives of elimination were 2.6, 2.9 and 2.8 h. The mean total, renal and extra-renal clearances amounted to 1237 ml/min, 149 ml/min and 1068 ml/min, respectively. The distribution coefficient was 3.5 l/kg, and protein binding amounted to 70% within the range of therapeutic concentrations. Absolute bioavailability was found to be approximately 50% by several different evaluation procedures. Thus, the pharmacokinetic profile of metipranolol shares features of both the lipophilic and the hydrophilic groups of β-blocking agents.
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  • 91
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 315-323 
    ISSN: 1432-1041
    Schlagwort(e): bendroflumethiazide ; propranolol ; hydralazine ; pharmacokinetics ; thin-layer chromatography ; fluorimetry ; fixed combination product
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Bendroflumethiazide (Bft) was administered to 6 healthy subjects at 3 different dose levels (2.5, 5 and 10 mg) in a cross-over design, either as capsules (2.5 mg) or as tablets (5 mg). Its pharmacokinetics were evaluated then and following administration of a fixed combination of Bft with propranolol and hydralazine to a further 7 volunteers. Plasma and urinary concentrations of Bft were determined by a new fluorimetric — thin-layer chromotography procedure. Peak plasma levels occurred after 2–3 h and averaged 15, 27 and 45 µg/l in the three dose groups. Areas under the plasma concentration — time curves (AUC0→12), which were 75, 147 and 250 µg l−1 h respectively, and cumulative urinary recovery (20%) were independent of the dose administered and the type of formulation. Thus Bft kinetics proved to be linear within the dose range evaluated. The plasma clearance was calculated to be 505 ml/min, renal clearance 108 ml/min and nonrenal clearance 396 ml/min. Bioavailability of Bft was not altered following administration of the fixed combination. The amount of propranolol found in the circulation did not change, whereas that of hydralazine (determined as apparent hydralazine) increased by 59% when the fixed combination was administered.
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  • 92
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 421-425 
    ISSN: 1432-1041
    Schlagwort(e): benzodiazepine ; lormetazepam ; lormetazepam glucuronide ; transfer to milk ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The concentrations of lormetazepam and its glucuronide in plasma and milk were determined during administration of 10 daily doses of lormetazepam 2 mg (2 tablets of NOCTAMID® - 1) to five mothers delivered by Caesarian section. Their babies were breast-fed throughout the study, and the plasma levels of lormetazepam and its glucuronide were determined three times in the babies. At 12 and 24h after administration, the plasma level of lormetazepam was about 3.5 ng/ml and 1.8 ng/ml in mothers, and below 0.09 ng/ml in the children. In milk the lormetazepam concentration was below 0.2 ng/ml. The plasma level of glucuronide varied between 24 ng/ml at 12h and 11 ng/ml 24h after administration. Almost no accumulation of unchanged lormetazepam was observed (factor: 1.3). The ratio of the levels of lormetazepam in milk and plasma was estimated to be below 0.06, and for the glucuronide the ratio was 0.04. The quantity of free and conjugated active ingredient transferred to the children via breast milk was calculated to be at most 100 ng/kg, corresponding to 0.35% of the maternal dose, which is regarded as tolerable.
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  • 93
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 499-504 
    ISSN: 1432-1041
    Schlagwort(e): gentamicin ; malnutrition ; pharmacokinetics ; infant
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of gentamicin was investigated in normal and malnourished infants aged 4–10 months. Neither mean “elimination” nor “distribution half life” show any difference, but the volume of distribution was higher in malnourished babies, probably due to their larger total body water.
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  • 94
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 423-428 
    ISSN: 1432-1041
    Schlagwort(e): pindolol ; renal failure ; metabolism ; pharmacokinetics ; 14C-pindolol ; blood metabolites ; urinary metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Increased metabolism of pindolol in renal impairment has previously been suggested by pharmacokinetic calculations. The present study was a pharmacokinetic and metabolic investigation in 7 patients with severe renal impairment (endogeneous creatinine clearance below 5 ml/min). All the patients received pindolol 5 mg t.d.s. 5 days. On the sixth day, after an overnight fast, 14C-pindolol 5 mg was given orally as a solution to drink. Blood samples were taken for up to 72 h and urine was collected at intervals up to 96 h for measurement of unchanged pindolol by a fluorimetric method and total radioactivity by liquid scintillation counting. Metabolites in blood and urine were analysed after separation by HPLC. It was found that the plasma levels following a single dose of 14C-pindolol were similar to those observed in healthy volunteers, but the elimination half-life was slightly increased up to 11.5 h. The observed steady state plasma concentrations of pindolol were twice as high but they are still in the therapeutic range of 10 to 100 ng/ml. Therefore, the dose of pindolol could have been reduced by a factor 2, but the reduction was not essential. No active metabolite of pindolol was found in plasma or urine, but elimination of the metabolites was decreased. The elimination half-life following multiple doses was prolonged compared to normal and it was quite comparable to that found for the pharmacodynamic half-life in renal patients. The discrepancy between the present findings and the previous results for metabolism and pharmacodynamic half-life was probably due to the sensitivity of the fluorimetric assay of pindolol.
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  • 95
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 155-160 
    ISSN: 1432-1041
    Schlagwort(e): amikacin ; pharmacokinetics ; development ; neonate ; infant ; child
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition kinetics of a single i.v. dose of amikacin was studied in 6 neonates (6–25 days old), 10 infants (4–18 months) and 8 young children (3–11 years). There was a progressive change in the distribution and elimination kinetics during development. The distribution coefficient of the antibiotic averaged of 0.429, 0.320 and 0.210 l/kg in the newborns, infants and young children, respectively and serum half-life (t1/2 β) in these three groups averaged 2.812, 1.803 and 1.196 h, respectively. Significant differences in certain pharmacokinetic parameters were found between the values in paediatric patients and in adults receiving the same dose. A linear relationship was established between the distribution volume of the antibiotic and the weight of the patients, as defined by the following equation: $${\text{Vd}}_{{\text{ss}}} \left( 1 \right) = 0.976 + 1.140 \cdot {\text{TBW}}\left( {{\text{kg}}} \right);r = 0.954$$ The results suggest that a regimen of very frequent administrations should be employed in infants and young children in order to maintain a therapeutic level throughout treatment.
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  • 96
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 22 (1982), S. 161-169 
    ISSN: 1432-1041
    Schlagwort(e): mebendazole ; hydatid disease ; Echinococcus granulosus ; hepatic disease ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentrations of mebendazole and its metabolites have been monitored in twelve patients after receiving a 10 mg/kg dose for cystic hydatid disease. The mebendazole plasma concentration-time profiles differed considerably between patients; elimination half-lives ranged from 2.8–9.0 h, time to peak plasma concentration after dosing ranged from 1.5–7.25 h and peak plasma concentrations ranged from 17.5 to 500 ng/ml. The mean peak plasma concentration of mebendazole after an initial dose (69.5 ng/ml) was lower than found in patients during chronic therapy (137.4 ng/ml). The plasma AUCTs for the major metabolites of mebendazole (methyl 5-(α-hydroxybenzyl)-2-benzimidazole carbamate and 2-amino-5 benzoylbenzimidazole) were about five times the plasma AUCT found for mebendazole in patients on chronic therapy. It is suggested that the slower clearance of these polar metabolites relative to mebendazole results from enterohepatic recycling. Since mebendazole is also highly plasma protein bound, caution should be observed in administering mebendazole to patients with liver disease. Concentrations of mebendazole found in the tissue and cyst material collected from two patients during surgery ranged from 59.5 to 206.6 ng/g wet weight.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 97
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 173-176 
    ISSN: 1432-1041
    Schlagwort(e): melperone ; neuroleptic drug ; dose dependent kinetics ; i.m. injection ; i.v. injection ; pharmacokinetics ; oral application
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of melperone (Buronil®, Ferrosan, Sweden) was studied after administration of various parenteral and oral doses to man. After parenteral administration, the data could be fitted to a two-compartment model, but after oral dosing the distribution phase could not be separated from the elimination phase, and so an one-compartment model gave the best fit. The half-lives were about 3–4 h, except after intramuscular injection, when the half-life was about 6 h. The bioavailability of oral doses was about 60% of the intravenous injection. After the highest oral dose of 100 mg, the pharmacokinetics, expressed as AUC or Cmax, showed non-linearity, possibly due to saturation of the hepatic elimination system.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 98
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 23 (1982), S. 331-333 
    ISSN: 1432-1041
    Schlagwort(e): ketoconazole ; vaginal candidosis ; oral antimycotic ; distribution ; pharmacokinetics ; vaginal tissue concentrations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma samples and biopsies of vaginal tissue were obtained from 23 healthy women undergoing operative sterilization, 1 to 6 h after a single oral dose of ketoconazole 200 mg. Drug concentrations in plasma and tissue, were measured by a specific gas chromatographic method. The vaginal tissue concentration averaged 2.4 times less than the corresponding plasma levels. Equilibrium between tissue, and plasma was established within 1 h after dosing, when vaginal tissue levels exceeded 1 µg/g. Ketoconazole concentrations decayed monoexponentially over the time interval studied (1–6 h), with the similar half-lives of 1.2 and 1.4 h in plasma and tissue, respectively. Following an oral 200 mg dose, a tissue concentration not less than 0.01 µg/ml was maintained over a 12 h period. This concentration has been shown to prevent outgrowth of the invasive (pseudo) mycelial form ofCandida albicans. Hence, a b.i.d. or t.i.d. dosage schedule of ketoconazole in vaginal candidosis would give continuously effective levels at the site of infection. Ketoconazole concentrations in vaginal fluid are thought to be much higher than in the tissue because of ion-trapping. The present data may explain the efficacy of oral ketoconazole in the treatment of vaginal candidosis.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 99
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 57-62 
    ISSN: 1432-1041
    Schlagwort(e): Amoxapine ; Amitriptyline ; antidepressants ; cholinergic functions ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the effects of single oral doses of amoxapine (100 mg and 200 mg), amitriptyline (50 mg and 100 mg), and placebo on some autonomic functions in ten healthy volunteers, using a balanced double-blind crossover design. Amitriptyline significantly reduced salivation and it significantly attenuated both miosis evoked by locally applied pilocarpine and sweat secretion evoked by locally applied carbachol. Amoxapine did not significantly alter any of these measures. Neither treatment significantly altered the pupillary light reflex (latency, amplitude, or 75% recovery time). Resting pupil diameter was significantly reduced by the higher dose of amoxapine but was not affected by the other treatments. The higher dose of amoxapine significantly increased supine systolic blood pressure, but did not affect heart rate or diastolic blood pressure; amitriptyline had no effect on any of these cardiovascular measures. These results confirm the antimuscarinic effects of amitriptyline in man, but provide no evidence for antimuscarinic effects of amoxapine.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 100
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 73-78 
    ISSN: 1432-1041
    Schlagwort(e): Thiamin ; thiamin monophosphate ; thiamin diphosphate ; distribution ; thiamin elimination ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The concentrations of thiamin and thiamin monophosphate and diphosphate in plasma and whole blood samples were assessed in six healthy subjects for 12 h and in urine for 24 h following an IV and PO bolus dose of 50 mg thiamin HCl. Unphosphorylated thiamin increased rapidly in plasma after IV administration and then decreased to its initial value within 12 h in all but one subject; the half-life was 96 min. Thiamin mono and -diphosphate increased moderately (56%), and decreased slowly; the half-life of diphosphate was 664 min. Within 24 h, 53% of the administered dose was recovered in the urine, indicating a restricted distribution. After oral administration, the peak thiamin concentration in plasma was reached after 53 min and the concentration then had increased to 179% of its initial value. The elimination half-life was 154 min, and only 2.5% of the given dose was recovered in the urine. The relative bioavailability of thiamin was 5.3%. A moderate amount of the administered thiamin was stored in blood. Other body tissues must play an important part, therefore, in the distribution of thiamin.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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