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  • bioavailability  (60)
  • Springer  (60)
  • American Institute of Physics
  • Nature Publishing Group
  • 1990-1994  (35)
  • 1980-1984  (25)
  • 1993  (35)
  • 1981  (25)
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  • Springer  (60)
  • American Institute of Physics
  • Nature Publishing Group
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  • 1990-1994  (35)
  • 1980-1984  (25)
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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nutrition 32 (1993), S. 2-20 
    ISSN: 1436-6215
    Schlagwort(e): Aminosäuren ; Proteine ; proteinhaltige Produkte, Bioverfügbarkeit, Biokinetik ; Technologie ; amino acids ; proteins ; protein-containing products ; bioavailability ; biokinetics ; technology
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: Summary To evaluate the bioavailability of amino acids from proteins and protein-containing products, the area under the postprandial plasma-concentration-time-curve of the amino acids after oral administration needs to be calculated. Therefore, basic values depending on circadian plasma concentration rhythms have to be subtracted from measured values after loading. To determine the relative bioavailability of two tested samples, e.g., a protein-containing product before and after processing or two technologically different preparations of the same protein, it is sufficient to compare their absorption-curves, both corrected by the basic values. For that purpose the mean value-curves corresponding to the group of subjects are used, because the individual courses show considerable differences, in particular due to discontinuous gastric emptying. Enzymatic hydrolysis of a lactalbumin reduces the quantitative bioavailability of the amino acids by 12%. Concerning products used in nutrition of patients and babies, the availability from ready-to-drink liquid products is about 7–10% better than that out of the same dry products in powdered form. Compared with sterilization, ultrahigh heat treatment of milk protein products improves the availability slightly, by about 1%. Processing of dried green peas destined for use in convenience food increases the protein availability by 20%.
    Notizen: Zusammenfassung Zur Bestimmung der Bioverfügbarkeit von Aminosäuren aus Proteinen und proteinhaltigen Produkten wird die Fläche unter der postprandialen Plasmakonzentrations-Zeit-Kurve der Aminosäuren nach oraler Zufuhr berechnet. Dies geschieht nach Subtraktion der durch zirkadiane Rhythmen bedingten Leerwerte von den gemessenen Plasmakonzentrationen. Zur Ermittlung der relativen Bioverfügbarkeit von zwei Testpartnern, z.B. einem proteinhaltigen Produkt vor und nach einer bestimmten Behandlung oder zwei technologisch verschiedenen Zubereitungen eines bestimmten Proteins, genügt der Vergleich der beiden bereinigten Resorptionskurven. Hierzu werden die entsprechenden Mittelwertkurven des Probandenkollektivs verwendet, da die individuellen Verlaufskurven insbesondere durch diskontinuierliche Magenentleerung erhebliche Verzerrungen aufweisen. Durch die enzymatische Hydrolyse verschlechtert sich die quantitative Bioverfügbarkeit der Aminosäuren bei einem Lactalbumin um zwölf Prozent. Bei Produkten für die Kranken- bzw. Säuglingsernährung ist die Verfügbarkeit aus fertigen Flüssigprodukten um sieben bis zehn Prozent verbessert gegenüber den gleichartigen Trockenprodukten in Pulverform. Bei ultrahocherhitzten Milcheiweißprodukten wird die Verfügbarkeit gegenüber einfach sterilisierten geringfügig um etwa ein Prozent verbessert. Durch die Präparation getrockneter grüner Erbsen für die Verwendung in Fertiggerichten wird die Verfügbarkeit des Proteins um zwanzig Prozent gesteigert.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Biodegradation 4 (1993), S. 141-153 
    ISSN: 1572-9729
    Schlagwort(e): bioavailability ; biodegradation ; sorption ; oil ; soil
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Energietechnik , Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    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
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    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
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    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.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 231-235 
    ISSN: 1432-1041
    Schlagwort(e): Carbamazepine ; kinetics ; population pharmacokinetics ; bioavailability ; controlled release ; non-linear model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absorption properties of a conventional tablet of carbamazepine (T) and a controlled release form of carbamazepine (TCR) have been compared using a nonlinear mixed effect model (NONMEM). Plasma carbamazepine concentration data were obtained from an open, steady-state, crossover bioavailability study in which 494 measurements were obtained from 13 patients, with an equal number of samples per patient for each dosage form. The pharmacokinetic model used was a one-compartment open model with first-order absorption and elimination. The objective function was used as a measure of the goodness of fit of the model to the data. Body weight was an important determinant of carbamazepine clearance (CL) but not volume of distribution (V). Accounting for the interindividual variability in volume of distribution did not significantly influence the objective function. Including different rates of absorption (ka) for the two dosage forms resulted in a significant improvement in the objective function, as well as reducing the interindividual variability in the rate of absorption. Adding a parameter for relative bioavailability (f) of TCR improved the objective function statistically, but an unrealistic value for V was obtained, and the absorption and elimination rates appeared to be transposed in the classical “flip-flop” manner. Fixing V to the value obtained before introducing f did not change the objective function and permitted estimation of f without the confounding influence of excessive parameters. The final population parameter estimates (standard error of estimate) were: CL, 0.0522 (0.0019) l·h−1·kg−1; V, 63.7 (FIXED)l; kaT, 0.312 (0.064) h−1; kaTCR, 0.149 (0.016) h−1; f, 1.01 (0.0326); variance (additive) in CL, 0.291 (0.083) (l·h−1·kg−1)2; residual intrasubject error variance (additive), 0.572 (0.082) (mg·l−1)2. The 95% confidence interval of the extent of absorption (f) of 93.6%–107.4% was well within the generally accepted range of ±20%, while the rate of absorption of Tegretol CR was significantly slower than that of Tegretol, as expected for a controlled release product.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    ISSN: 1432-1041
    Schlagwort(e): Prednisone ; Prednisolone metasulfobenzoate ; bioavailability ; intestinal infusion ; absorption ; presystemic clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The role of intestinal absorption in the differential availability of prednisone (PN) and prednisolone metasulfobenzoate (PO-MS), which might account for clinical resistance to PO-MS, has been studied by an infusion technique. In a randomized cross-over design trial, a solution in isotonic saline of PN or PO-MS (115 mg·l−1 was infused at 5 ml·min−1 for 2 h, into a 25 cm segment of jejunum in 8 healthy fasting subjects. The intestinal content was partly collected and the flow rate at the end of the test segment was determined by using a water movement marker (PEG 4000). Plasma, intestinal and urine concentrations of PN and PO were determined by liquid chromatography. From the data on PO, the active molecule, the systemic availability of PO-MS was significantly smaller than of PN, with the respective mean AUCs being 1.71 and 3.60 mg·h−1. The difference was associated with smaller mean Cmax, 0.20 vs 0.64 mg·l−1, higher mean tmax, 2.94 vs 2.06 h and lower mean ka, 0.98 vs 2.18 l/h after PO-MS. No significant difference was found in the half-life or renal clearance of the formulations tested. The mean MRT was significantly increased after PO-MS, 6.82 vs 5.30 h. The observed difference probably reflected a difference in intestinal absorption. The mean absorption in the test segment of PO-MS was significantly smaller at 17.4 vs 85.5% for PN. The ester form may be a limiting factor in the intestinal absorption of PO. Therefore, the choice of PN or PO-MS should follow the therapeutic indication, depending on whether a major systemic effect or a prolonged intestinal local effect is preferred.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 251-258 
    ISSN: 1432-1041
    Schlagwort(e): medigoxin ; digoxin ; dissolution rate ; proportionality ; bioavailability ; prediction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We compared our ability to predict the dose of medigoxin and of digoxin required to achieve a fixed serum concentration (the dose requirement) in 33 outpatients. Preliminary work supported the assumptions that the steady state glycoside concentration achieved was proportional to the daily dose given to an individual, and that the bioavailability of the different tablet presentations was similar for either glycoside. We were not able to predict the dose requirement from patient characteristics with any more certainty for medigoxin than for digoxin. Not only the between-patient variability in dose requirement, but also the within-patient variability, was similar for the two glycosides. However the digoxin used had a dissolution rate of over 90% in 1 h. When comparing medigoxin with digoxin of lower, or more variable dissolution rate, medigoxin may be preferable.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 53-55 
    ISSN: 1432-1041
    Schlagwort(e): digoxin ; bioavailability ; dose-dependency ; urinary excretion ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Nine healthy volunteers received single 0.25, 0.5, 1.0, 1.5, and 2.0 mg doses of oral digoxin tablets in random sequence on five occasions separated by at least 4 weeks. Urinary excretion of immunoassayable digoxin was determined from 8 consecutive 24 h urine samples collected after each dose. Mean values of cumulative urinary excretion of digoxin at the 5 doses were: 40.9, 35.6, 36.4, 34.1, and 33.5% of the dose (F=0.64; d. f.=4.32; N. S.). Mean values of urinary excretion half-life were: 2.48, 2.03, 2.20, 2.07, and 1.87 days (F=2.87; d. f.=4.32;p=0.05). Thus, the bioavailability of orally administered digoxin tablets in healthy volunteers is dose-independent over an 8-fold range of doses.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 287-292 
    ISSN: 1432-1041
    Schlagwort(e): diacetolol ; acebutolol ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and bioavailability of diacetolol, the principal metabolite of acebutolol, were studied in 6 healthy subjects. Plasma concentrations were determined following a single intravenous injection of diacetolol 100 mg and three oral doses of diacetolol 100, 400 and 800 mg, in random order. The average oral bioavailability of diacetolol was F: 0.302±0.052 (100 mg), 0.363±0.052 (400 mg) and 0.426±0.068 (800 mg); the differences are not significant. The mean plasma half-life of the terminal phase, 7.94±0.26 h after intravenous administration, was significantly higher than after oral administration 12.27±1.00 h (100 mg), 12.82±1.59 h (400 mg) and 13.05±1.22 h (800 mg) (p〈0.02 to 0.05); the mean urine half-lives of the terminal phase were not significantly different. Renal clearance of diacetolol 10.2±0.81·h−1 represented about two-thirds of total body clearance 15.9±1.21·h−1. The results suggest either a first-pass effect or incomplete absorption of diacetolol after oral administration.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 305-307 
    ISSN: 1432-1041
    Schlagwort(e): ketoprofen ; aluminium phosphate ; bioavailability ; antacid ; pharmacokinetics ; interaction study
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The purpose of this study was to determine whether a concomitant single dose of antacid (aluminium phosphate), or multiple doses of this antacid, administered prior to and with ketoprofen would alter the bioavailability of this non steroidal anti-inflammatory agent. The possible effects of aluminium phosphate were evaluated following administration of ketoprofen alone (Phase I), co-administration of antacid and ketoprofen (Phase II), and antacid for four days before administration of ketoprofen with co-administration on the day of the study (Phase III). There were no significant differences between treatment means for peak plasma concentration, time to peak plasma concentration, and area under the plasma concentration-time curve. The observed differences were due only to individual effects. The results indicate a lack of interaction between ketoprofen and the antacid aluminium phosphate (Phosphalugel)
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 359-365 
    ISSN: 1432-1041
    Schlagwort(e): tolfenamic acid ; anti-inflammatory agent ; human pharmacokinetics ; bioavailability ; intravenous administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent was studied in six healthy volunteers after an intravenous dose of 100 mg and oral doses of 100, 200, 400 and 800 mg. The disposition of intravenous tolfenamic acid could be described by two-compartment open model, with a central compartment volume (Vdc) of 5.6±0.31 (mean±SE), volume during β-phase (Vdβ) of 31±21, and a total elimination rate constant (k10) 1.6±0.1 h−1. The terminal elimination half-life was 2.5±0.6 h and the total plasma clearance 155±15 ml/min. The elimination occured principally by extrarenal mechanisms, the recovery of unchanged drug together with is glucuronide in urine averaging only 8.8% of the intravenous dose. The binding of tolfenamic acid to plasma proteins averaged 99.7%. The gastrointestinal absorption had a mean half-life of 1.7±0.1 h. Based on comparison of areas under the plasma concentration time-curves after intravenous and oral administration, the biovailability of tolfenamic acid capsules averaged 60%. The rate and extent of absorption and the rate of elimination of tolfenamic acid were independent of dose.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 65-72 
    ISSN: 1432-1041
    Schlagwort(e): tranexamic acid ; pharmacokinetics ; bioavailability ; oral absorption ; influence of food ; plasma clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Tranexamic acid 1 g was given intravenously to three healthy volunteers. Plasma concentrations decayed in three monoexponential phases. Most elimination took place during the first eight hours, giving an apparent elimination half-life of approximately two hours. Plasma clearance ranged between 110–116 ml/min. The urinary recovery of tranexamic acid exceeded 95% of the dose. Ten healthy volunteers were given tranexamic acid 2 g orally on an empty stomach, and together with a meal. Food had no influence on the absorption of tranexamic acid, as judged by comparison of the peak plasma concentration, the time required to reach the peak, the AUC from zero to six hours, and the urinary excretion data. The oral bioavailability of tranexamic acid, calculated from 24 h urinary excretion after oral and intravenous administration, was 34% of the dose.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 277-282 
    ISSN: 1432-1041
    Schlagwort(e): dexamethasone phosphate ; dexamethasone sulphate ; intravenous injection ; bioavailability ; pituitary-adreno-cortical suppression ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The metabolic fate and ACTH-supressant activity of two injectable dexamethasone esters, 21-phosphate and 21-sulphate, were studied in healthy men. After i.v. injection of 20 mg free steroid alcohol, dexamethasone phosphate was efficiently hydrolyzed to free dexamethasone, reaching its peak plasma concentration within 5 min. About 9% of the administered dose appeared in the urine as free dexamethasone. By contrast, virtually no free dexamethasone was found in plasma and urine after injection of dexamethasone sulphate. Pharmacokinetic analysis showed that dexamethasone sulphate had a shorter plasma half-life and a higher metabolic clearance rate than free dexamethasone. A larger fraction (60%) of dexamethasone sulphate was rapidly excreted unmetabolized in urine. The plasma cortisol level was significantly suppressed for more than 24 h after dexamethasone phosphate, while the plasma cortisol profile after dexamethasone sulphate merely showed physiological circadian variations. When the steroid esters were injected after pretreatment with metyrapone, a definite suppression of plasma ACTH was noted after dexamethasone phosphate, but again, dexamethasone sulphate was ineffective. These results cast serious doubt on the clinical value of dexamethasone sulphate as an injectable glucocorticoid, and critical reevaluation of this preparation is needed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 465-471 
    ISSN: 1432-1041
    Schlagwort(e): metoclopramide ; pharmacokinetics ; bioavailability ; first-pass effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The time courses of plasma metoclopramide concentrations were followed in six subjects after oral and intravenous single dose administration. Plasma concentration-time data following i.v. administration in each subject were found to fit a two compartment model with a mean terminal half-life of 4.55 h±0.80 h and a mean distribution half-time of 0.35 h±0.09 h. Volumes of distribution were high (3.43±1.181 · kg−1), and clearances (0.53±0.191 · kg−1h−1) approached liver plasma flow. This suggests that metoclopramide occurs at higher concentrations in tissues than in plasma, and that its clearance is probably limited by liver blood flow rather than liver metabolic capacity. The post-absorption decline in metoclopramide plasma levels after oral administration was also biexponential in each subject. The terminal half-life was 5.17 h±0.98 h. Mean volume of distribution and mean clearance were similar to intravenous values (after adjustment for bioavailability). Oral absorption was rapid with peak plasma concentrations being reached at a mean time of 0.93 h. A mean bioavailability of 0.77 was calculated for the six subjects, and it was postulated that this incomplete availability is due to a first-pass effect. The inter-individual variation in the degree of ‘first-pass’ was considerable (0.47–1.14).
    Materialart: Digitale Medien
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 473-478 
    ISSN: 1432-1041
    Schlagwort(e): methadone ; bioavailability ; pharmacokinetics ; single dose ; stable isotope technique ; two compartment model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of methadone was studied in eight opiate dependent subjects during detoxification. Plasma concentrations were determined by mass fragmentography for 48 hours after administration of methadone 20 mg as tablets and simultaneous intravenous injection of deuterium-labelled methadone 20 mg. Pharmacokinetic parameters were calculated for the intravenous dose assuming a two compartment open model. Bioavailability was determined by comparing the areas under the plasma concentration versus time curves of unlabelled and labelled methadone. The beta-phase plasma half-lives varied five-fold, with a range from 8.5 to 47 h. The apparent volumes of distribution varied from 2.1 to 5.61/kg. Five patients had a bioavailability exceeding 90%, and three had lower bioavailabilities of between 41 and 76%. The unlabelled and labelled drug appeared to be pharmacokinetically equivalent. The data show that for a majority of these subjects the bioavailability was higher than 45%, the previously reported value. The marked individual variation in methadone pharmacodynamics and kinetics, and the possibilities both of cellular and methabolic tolerance, require an individually optimized dosage regimen.
    Materialart: Digitale Medien
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  • 17
    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
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  • 18
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 387-388 
    ISSN: 1432-1041
    Schlagwort(e): Iron deficiency anaemia ; Phenytoin ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Iron deficiency is a common nutritional deficiency, which leads to structural functional and enzymatic changes in the body that may affect the pharmacokinetics of drugs. The present study in 7 normal volunteers and 8 adult male patients with irondeficiency anaemia (IDA) was done to investigate the effect of iron deficiency and its treatment with total dose iron (TDI) on the bioavailability of a single dose of phenytoin. Phenytoin bioavailability was investigated before and 3 and 28 days after TDI. The bioavailability parameters Cmax, tmax, AUC and 2 h phenytoin concentrations were not significantly different in anaemic patients as compared to normal volunteers before or after treatment, except for an increase in tmax 28 days after TDI treatment.
    Materialart: Digitale Medien
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 575-578 
    ISSN: 1432-1041
    Schlagwort(e): Pantoprazole ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma pharmacokinetics of pantoprazole have been investigated following single intravenous infusion and single oral administration at a dose of 40 mg to 12 healthy male subjects in a randomised cross-over study. Both treatments were generally well tolerated and no relevant compound-related adverse events were noted. The plasma pharmacokinetics of pantoprazole following intravenous infusion in this group of subjects were characterised by a total plasma clearance of 0.13 l·h−1·kg−1 and apparent terminal elimination half-life 1.9 h. The apparent volume of distribution estimated at steady state (0.171·kg−1) was compatible with the localization of a major fraction of the compound in extracellular water. Following oral administration as an enteric-coated tablet formulation, a variable onset of absorption was followed by rapid attainment of maximum plasma concentrations of pantoprazole. Pantoprazole was well absorbed following oral administration; the absolute systemic bioavailability of the compound was estimated as 77% (95% CI, 67 to 89%).
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  • 20
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 579-582 
    ISSN: 1432-1041
    Schlagwort(e): 2-Chloro-2′-deoxyadenosine (CdA) ; omeprazole ; food ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of oral CdA (0.24 mg/kg) was studied in 4 patients (1 with hairy cell leukaemia and 3 with B-cell chronic lymphocytic leukaemia) to determine any effect of food and fasting with and without omeprazole. Food intake did not significantly influence the bioavailability of CdA (42% after food intake vs 46% while fasting) but it did reduce the maximum plasma concentration (Cmax) by 40%; 83 compared to 116 nM while fasting. The time to reach maximum concentration (tmax) was delayed about 0.8 h after food intake. Pretreatment with omeprazole did not significantly influence the bioavailability of CdA (51% vs 46% without), or the interindividual variability in bioavailability in the fasting state (C.V. 0.26 with and C.V. 0.27 without). In conclusion, there was a small, though not statistically significant reduction in the bioavailability of CdA after food intake. Omeprazole did not significantly improve the bioavailability of CdA.
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  • 21
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 79-84 
    ISSN: 1432-1041
    Schlagwort(e): Tiopronin ; 2-Mercaptopropionylglycine ; bioavailability ; urinary excretion ; cystine urolithiasis ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ten healthy subjects were given 500 mg (3064 μmol) tiopronin, or 2-mercaptopropionylglycine (2-MPG) by mouth. Cmax was reached after 3–6 h, and after a shorter β-phase a long terminal half-life of 53 h of total tiopronin was found. Tiopronin measured as unbound (non-protein-bound) drug disappeared more rapidly from plasma, with a calculated t 1/2 of 1.8 h. Mean residence time was higher (58 h) when calculated as total tiopronin than as unbound tiopronin (6 h), and this was also the case for the volume of distribution (Vλ=4551 vs Vλ,u=41 1). The results indicate extensive protein binding in plasma and a deep pool of tissue bound tiopronin after the first absorption and distribution phases. Absolute bioavailability (f) was 63%, and bioavailability calculated from urinary excretion was 47%, which are well correlated with each other. Urinary excretion was mainly confined to the first 6 h (74%) and was almost complete (98%) within 12 h. We conclude that the maximal absorption of the tiopronin was late, protein and tissue binding of the drug were high and its bioavailability varied. The renal excretion of low molecular weight tiopronin occurred early, which implies that the drug should be given in divided doses, at least twice daily, for optimal efficiency in the treatment of cystinuria.
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  • 22
    ISSN: 1432-1041
    Schlagwort(e): verapamil ; pharmacokinetics ; bioavailability ; hepatic first-pass metabolism ; stable isotopes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Following i. v. administration, the plasma concentration-time curve of verapamil could best be described by either a mono- or biexponential equation. Total plasma clearance (1.26 l/min) approached liver blood flow (1.5 l/min), so it can be concluded that its clearance is liver blood flow-dependent. Although absorption was almost complete after oral administration, absolute bioavailability (20%) was low, due to extensive hepatic first-pass metabolism. The approach using stable isotope-labelled and unlabelled drug permits simultaneous administration by the intravascular and extravascular routes, thus allowing determination of absolute bioavailability in a single experiment.
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 149-155 
    ISSN: 1432-1041
    Schlagwort(e): proxyphylline ; asthma ; pharmacokinetics ; bioavailability ; healthy adults ; theophylline derivative
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Serum concentrations and urinary excretion of proxyphylline have been measured in five healthy adults after intravenous (29 µmol/kg), single oral (21 µmol/kg) and multiple oral (21 µmol/kg three times a day) doses to produce steady state. The mean peak time after oral administration was 29 min. The mean fraction absorbed was 1.09 calculated from serum concentrations, and 1.05 calculated from urinary excretion of the drug. The apparent volume of distribution was 0.61 l/kg (0.53–0.72 l/kg), 26% higher in males than in females. A two-compartment open model was found to describe the decline in the serum concentrations, giving a mean distribution half-life of 6 min. The intersubject ranges of biological half-life were 8.1–12.1 h and 8.3–12.6 h calculated from serum and urine data, respectively. 24% (18–29%) of the dose was excreted unchanged in urine, which agreed with the relationship between the calculated total body clearance and the renal clearance of the drug.
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 343-347 
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; phenobarbital ; gastro-intestinal absorption ; bioavailability ; renal clearance ; non-renal clearance ; enzyme induction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of orally administered cimetidine was studied in 8 healthy subjects before and after 3 weeks of treatment with phenobarbital 100 mg daily, and in a separate study 4 subjects received cimetidine intravenously before and after the administration of phenobarbital. There was no change in the volume of distribution, but total plasma clearance was increased by a mean of 18%, mainly due to a 37% increase in nonrenal clearance. Renal clearance and half-life were not significantly altered. The area under the plasma concentration-time curve after oral administration was significantly (P≪0.05) reduced by a mean of 15% after phenobarbital treatment. The amount of cimetidine excreted in urine and its sulphoxide metabolite were significantly (P〈0.05) reduced, on average by 34% and 26%, respectively by phenobarbital treatment. The data indicate that an apparent 20% reduction in the absorption of cimetidine was due to induction of gastrointestinal metabolism of cimetidine, with some contribution also from hepatic metabolism. Reduced absorption per se could not be totally excluded. Although the magnitude of the change was small, the finding of an 11% decrease in the time to achieve an effective plasma level of cimetidine after phenobarbital treatment may contribute to the ineffectiveness of cimetidine in certain patients.
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  • 25
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 449-452 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; ethylenediamine ; suppository ; serum concentration ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absorption of theophylline from a suppository not containing ethylenediamine was tested in 9 healthy volunteers. AUC after rectal administration of anhydrous crystalline theophylline 250 mg (AUCrectal) was compared with the AUC after oral administration of microcrystalline theophylline 250 mg (Nuelin®; AUCoral) in a randomized, cross-over study. The ratio AUCrectal/AUCoral was 0.75 at 10 h, and the ratio AUCrectal×βrectal/AUCoral×βoral extrapolated to infinite time was 0.83. A mean concentration of 5.7 µg/ml was reached 3.7 h after a single rectal dose. The absorption studies were performed with suppositories stored for 15 weeks at 22 °C. No effect on the in vitro release rate of theophylline from the suppository was observed during storage at room temperature from 3 to 31 weeks after production. Since aminophylline suppositories are known to decompose upon storage, the results suggest that a formulation without ethylenediamine is preferable for the rectal administration of theophylline.
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  • 26
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 459-463 
    ISSN: 1432-1041
    Schlagwort(e): buflomedil ; vasodilatation ; pharmacokinetics ; bioavailability ; vasoactive drug
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A dose-ranging pharmacokinetic study of buflomedil was carried out in eight subjects to determine the pharmacokinetic parameters of the drug after oral and intravenous administration. Based on AUC∞ analyses, the pharmacokinetics of buflomedil were found to be linear within the dose ranges studied (50 to 200 mg for i. v. injection and 150 to 450 mg for oral administration). In the oral study, the mean biological half-life of the drug was 2.97 h, while after intravenous dose it was 3.25 h. The apparent volume of distribution after the pseudodistribution equilibrium (Fdβ) and volume of distribution at the steady state (Vdss) were 1.43±0.24 l/kg and 1.32±0.26 l/kg, respectively. The mean urinary recovery of intact drug and the metabolite, paradesmethyl buflomedil, after intravenous dosing, were 23.6% and 18.7%, respectively, while after oral dosing, they were 18% and 14.8%, respectively. On the average, 72% of the dose was obserbed into the systemic circulation after oral administration. This level of bioavailability was attributed to the hepatic first-pass effect.
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  • 27
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 44 (1993), S. 493-495 
    ISSN: 1432-1041
    Schlagwort(e): Timolol ; β-adrenoceptor antagonist ; transdermal ; percutaneous absorption ; skin ; pharmacokinetics ; bioavailability ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic profiles of transdermal timolol 6 and 24 mg (as 5 and 20% w/v patches) was studied in four healthy young volunteers. To assess its bioavailability, the pharmacokinetics of an IV infusion of timolol maleate 5 mg was also determined in the same subjects. When the 20% (w/v) timolol patch was applied, the mean bioavailability was 74.4%. Plasma timolol concentrations were below the detection limit when a 5% patch was applied to the same skin area in all four subjects, except for one in whom the bioavailability was 23.6%. Weak erythema developed at the application site in all of the volunteers after application of the 20% (w/v) patch. However, erythema did not develop in any volunteer when the 5% patch was applied. The β-blocking effect was determined by exercise testing. Similar plasma levels generated similar changes in exercise-induced heart rate after the transdermal and intravenous administration of timolol.
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 45 (1993), S. 169-172 
    ISSN: 1432-1041
    Schlagwort(e): Fenspiride ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absolute bioavailability of fenspiride has been studied in twelve healthy volunteers. It was administered IV and orally in single doses of 80 mg fenspiride hydrochloride according to a randomised crossover pattern. Following IV administration, the plasma clearance of fenspiride was about 184 ml·min−1, and its apparent volume of distribution was moderately large (2151). When given orally as a tablet, fenspiride exhibited fairly slow ab- sorption; the maximum plasma concentration (206 ng·ml−1) was achieved 6 h after administration. The absolute bioavailability was almost complete (90%). The tablet had slow release characteristics. The elimination half-life obtained from the plasma data was 14 to 16 h independent of the route of administration.
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 19 (1981), S. 225-230 
    ISSN: 1432-1041
    Schlagwort(e): fluoride ; sustained release tablets ; serum concentration ; urinary excretion ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Various sodium fluoride tablets used for the treatment of osteoporosis were evaluated. The tablets were characterized in vitro by determining the release curves. The serum levels and urinary recovery of fluoride were determined after a single oral dose either of rapidly soluble (conventional), sustained release or enterocoated tablets. The in vivo study showed that administration of sustained release tablets eliminated high serum peaks and prolonged the duration of an elevated serum level as compared to conventional tablets. The biovailability of the fluoride was lower after intake of sustained release and enterocoated tablets, and there was an increase in the interindividual variance of biovailability.
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 53-58 
    ISSN: 1432-1041
    Schlagwort(e): hydralazine ; food ; absorption ; plasma level ; salivary level ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Single oral doses of hydralazine (Apresoline) 50 mg were administered on two occasions to eight healthy volunteers when fed and fasting. Blood and saliva samples were taken at intervals after dosing and analysed for drug. Heart rate and blood pressure were measured before and at intervals after dosing, at rest, after tilt and exercise. Plasma hydralazine levels showed wide inter-individual variation. The areas under the plasma concentration-time curve (0–8 h), the height of the peak plasma levels and the time to peak were not significantly different between the fed and fasting state. Salivary hydralazine levels were readily measurable but showed little correlation with plasma levels. The heart rate and pulse pressure were increased after drug both at rest, supine and erect, and after exercise for between 6 and 8 h.
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 127-133 
    ISSN: 1432-1041
    Schlagwort(e): ketoprofen ; pharmacokinetics ; multipledose ; bioavailability ; assay ; modelling
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A commercial capsule containing 50 mg of ketoprofen (Orudis), a simple capsule containing 50 mg of ketoprofen alone and 50 mg of ketoprofen in an aqueous solution were given as separate doses in a randomized sequence to 12 normal adult males. The areas under the resulting plasma concentration-time curves (AUC) were remarkably consistent for each volunteer. The bioavailability from the commerical capsule relative to that from the solution was 99.7%±10.5% and that from the simple capsule was 102%±10%. After 6 of the volunteers had taken the commercial capsule 6 hourly for thirteen doses, their AUC extrapolated to infinity was significantly higher (by 22%) than that after the single dose indicating, contrary to previous reports, accumulation upon multiple dosing. The interdose AUC after the thirteenth dose was, however, statistically indistinguishable from the AUC-to-infinity after the single dose as might be expected from linear kinetics. The ketoprofen solution generated peak plasma concentrations in only one-third the time (21±7 min) required for the capsules (commercial, 72±45; simple, 61±39 min). Despite plasma concentrations being tracked over a 200-fold range, log linearity was not established within 12 h in any of the 42 profiles obtained. A two-compartment open model was fitted to the solution data giving excellent prediction of the time-to-peak and clearance (Cl/F=5.2±1.1 l/h) as determined by eye and by log-trapezoidal rule, respectively.
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  • 32
    ISSN: 1432-1041
    Schlagwort(e): zimelidine ; norzimelidine ; antidepressant ; pharmacokinetics ; bioavailability ; urinary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five healthy adults were administered zimelidine orally (150 mg) and by intravenous infusion (20 mg) in a crossover design. Blood and urine samples were collected for a period of 28 hours after dosing and the concentrations of zimelidine and norzimelidine determined. There was no significant difference in terminal phase half-life of zimelidine after oral (4.7 h±1.3 SD) or intravenous dosing (5.1 h±0.7 SD). An average of 50% of the ingested oral dose reached the systemic circulation. Excretion of unchanged zimelidine in urine was on average 1.26% of the intravenous dose. In appears that zimelidine is completely absorbed from the gastrointestinal tract and “first-pass metabolism” in the liver reduces the bioavailability to 50%. The mean plasma half-life for norzimelidine was 22.8 h. The area under the plasma concentration time curve for norzimelidine after oral administration was 92% of that after intravenous administration. The plasma concentration of both zimelidine and norzimelidine are predicted to approach steady-state within 3–5 days.
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  • 33
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 20 (1981), S. 225-228 
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; antacids ; metoclopramide ; absorption ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 8 healthy subjects the absorption of cimetidine was investigated when given alone, together with 60 ml aluminium/magnesium hyroxyde containing antacid (neutralising capacity 26 mmol HCl/10 ml), and together with liquid metoclopramide 14 mg. The antacid significantly (P〈0.01) reduced the bioavailability (area under the plasma level-time curve) of cimetidine, on average by one third. Metoclopramide also reduced the bioavailability by an average of 22%. The reductions were associated with significantly reduced excretion of cimetidine in urine. There was no change in the half-life or renal clearance of cimetidine, supporting the hypothesis of reduced gastrointestinal absorption. The results indicate that cimetidine and antacids should not be given together, and that the dose of cimetidine may have to be increased if it is administered concomitantly with metoclopramide.
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  • 34
    Digitale Medien
    Digitale Medien
    Springer
    Aquatic ecology 27 (1993), S. 189-195 
    ISSN: 1573-5125
    Schlagwort(e): heavy metals ; biomonitoring ; bioavailability ; Enteromorpha intestinalis ; Weser estuary
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The present study was planned to assess the validity ofEnteromorpha intestinalis for an active biomonitoring of heavy metals in the Weser estuary. Exposure of cultured algae (active biomonitoring) was carried out in 1987 and 1988, simultaneouslyEnteromorpha spp. was collected from the banks (passive monitoring) in the estuary. Cd, Pb, Ni, Zn and Cu contents of exposed algae were higher than the metal content of collected algae. Metal contents of both collected and field algae varied significantly over space and time. Bioconcentration factors and results of linear regression analysis indicate, that the bioavailability of Cu and Ni varies with regard to the sampling location but cannot be calculated from heavy metal concentration in the water. Due to the different metal and species specific bioavailability, we want to stress the need to monitor contamination of organisms directly. An active biomonitoring usingE. intestinalis will establish a rationale to compare contamination of different estuaries.
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 21 (1993), S. 195-208 
    ISSN: 1573-8744
    Schlagwort(e): bioavailability ; phenytoin ; Michaelis-Menten kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The bioavailability of capsules of phenytoin was determined by two methods: a method involving the numerical integration of the Michaelis-Menten equation and an alternative method involving fitting the time course of plasma concentrations, following the administration of the reference intravenous dosage, to an empirical quadratic function of time. The latter procedure requires much simpler computations. The two methods yielded very similar estimates of the rate and extent of absorption of phenytoin. Total absorption was 0.90±0.05 and 0.89±0.05(x±SE, n=6)using the methods of numerical integration and quadratic curve fitting, respectively. Both methods indicated that the rate of absorption of phenytoin was inconsistent and slow. Half the total absorption of phenytoin occurred over 2.5 ±0.3 hr but the remainder was absorbed very slowly over a period of about 30 hr. Empirical functions may be more generally useful in the determinations of the bioavalability of drugs, particularly if some aspects of the disposition are saturable.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 10 (1993), S. 239-242 
    ISSN: 1573-904X
    Schlagwort(e): vitamin C ; ascorbic acid ; disintegration ; dissolution ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The goal of this study was to examine if the current USP disintegration standard for vitamin C tablets (max. 30 min in water at 37°C with disks) is adequate or if a tighter disintegration standard (e.g., European compendia max. 15 min) should be recommended based on bioavailability considerations. Four formulations of 500-mg vitamin C tablets ranging in mean disintegration time from 9 to 120 min were compared with a standard vitamin C solution in a double-blind clinical trial with 15 subjects. The products were administered with a standard breakfast. The data show that a solution of vitamin C and a fast-disintegrating tablet (8–9 min) have equal but significantly lower bioavailability than tablets with longer disintegration times (30, 60, 120 min). Tablets with a mean disintegration time of 60 min showed the highest bioavailability. When the disintegration test was performed without disks, disintegration times increased so much that only the tablets with the fastest disintegration time (which were also the tablets with the lowest bioavailability) met the current USP disintegration time limit. Based on the results of the study, changes in the USP standard to omit the disks or to shorten the disintegration time will not achieve enhanced bioavailability but will result in reduced vitamin C absorption. In vitro dissolution of vitamin C tablets did not show the traditional relationship with bioavailability.
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  • 37
    ISSN: 1573-904X
    Schlagwort(e): pharmacokinetics ; oral absorption ; double peaks ; absorption interaction ; intestinal excretion ; bioavailability ; dose dependency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Pafenolol is a β-blocker with unusual oral absorption properties. The blood concentration–time profile exhibits two peaks, and the bioavailability is low and dose dependent because of incomplete and nonlinear intestinal uptake. We addressed the question whether the intestinal absorption of pafenolol was affected by bile depletion in the gut lumen of rats. Further, the hypothesis that variable gastric emptying accounts for double peaks in blood was tested by duodenal administration of pafenolol. Following intraduodenal administration to rats with intact bile secretion, double peaks were observed in the blood concentration–time curve. The bioavailability was 6.8 ± 0.7% for the low dose (1 µmol/kg) and increased significantly to 28 ± 10% following the high duodenal dose (25 µmol/kg). These blood concentration–time profiles exclude interrupted gastric emptying as cause of the twin peaks. In bile duct-cannulated rats the intestinal absorption of the low dose (1 µmol/kg) was still poor (F = 10.7 ± 5.5%) and the blood concentration–time profile contained two peaks. Following administration of a high duodenal dose (25 µmol/kg) to rats with an almost bile-free small intestine, the absorption rate increased and the double-peak phenomenon disappeared in five of seven rats, while the bioavailability increased significantly, to 62 ± 27%. These results suggest that the low bioavailability of pafenolol is due to a complexation between bile and pafenolol in the gut lumen, preventing intestinal uptake in the major part of the small intestine. Further, such complex formation in the intestinal lumen may be the underlying mechanism of the double peaks observed in the blood concentration–time profile.
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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 10 (1993), S. 588-592 
    ISSN: 1573-904X
    Schlagwort(e): theophylline ; sustained release ; bioavailability ; deconvolution ; in vivo/in vitro correlation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A novel multiparticulate sustained-release theophylline formulation, which consisted of spherical drug pellets coated with a rate-controlling membrane, was evaluated in vivo. Two preparations that differ solely in the coat thickness, and hence rate of in vitro drug release, were studied in comparison with a solution of the drug. Both preparations produced serum concentration profiles that are reflective of a slow and sustained rate of absorption. The in vivo release versus time profiles calculated using a deconvolution procedure showed that the two preparations differed in the rate but not the extent of drug release. Satisfactory correlation was also obtained between the in vivo and the in vitro results. When the two preparations were further compared using the parameters, time to reach peak concentration (T p), peak concentration (C p), and total area under the serum concentration versus time curves (AUC), a statistically significant difference was observed in the T p and C p values but not the AUC values, suggesting that the preparations differed in the rate but not the extent of absorption. In addition, the extent of absorption from both preparations was comparable to that obtained with the drug solution.
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  • 39
    ISSN: 1573-904X
    Schlagwort(e): procaterol ; bronchodilator ; healthy volunteers ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The pharmacokinetics and relative oral bioavailability of procaterol, an orally active β2-adrenergic agonist bronchodilator were evaluated in healthy volunteers. Procaterol was rapidly absorbed after oral administration. Mean plasma procaterol concentration–time profiles and pharmacokinetic parameters for both formulations were essentially superimposable. Following tablet administration, the mean C max was 358 pg/mL and the corresponding mean t max was 1.6 hr. Mean renal clearance was 163 mL/min and accounted for approximately one-sixth of the mean apparent oral plasma clearance (988 mL/min). The mean apparent elimination half-life of procaterol was 4.2 hr. Hepatic metabolism appears to be the primary mechanism for elimination of procaterol from the body, and first-pass metabolism may limit systemic bioavailability.
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  • 40
    ISSN: 1573-904X
    Schlagwort(e): remoxipride ; modified release ; suspension ; bioavailability ; convolution ; deconvolution ; dissolution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Remoxipride, a D2-dopamine receptor antagonist, is well tolerated and completely absorbed after oral administration. Because of its extremely bitter taste, an oral palatable suspension was developed by using a taste-masking microencapsulation. The bioavailability of remoxipride was investigated in two studies in healthy volunteers after administration of a 100-mg dose in suspension. The first study used a capsule as reference, and the second study a plain solution. Taste assessment was carried out in the second study. The extent of bioavailability was the same when comparing the oral suspension to a capsule and to a plain solution. However, the rate of absorption is delayed, and Tmax was 3.0 hr after the suspension, 1.0 hr after the oral solution, and 1.6 hr after the capsule. The release rate in vitro from the suspension was determined by applying the USP-paddle method. By using numerical convolution and deconvolution, the release rates in vivo and in vitro were shown to be similar when using water with 0.5% sodium lauryl sulfate as dissolution liquid. The taste-masked oral suspension is suitable for full-scale production, with good control of the encapsulation process and of the preparation of a suspension.
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  • 41
    ISSN: 1573-904X
    Schlagwort(e): ranitidine ; effervescent tablet ; absorption ; bioavailability ; bioequivalence ; sodium acid pyrophosphate ; gastrointestinal transit time
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract During development of a ranitidine effervescent oral solution dosage form, a marked decrease was observed in the extent of ranitidine absorption relative to the conventional oral tablet. Two studies were conducted in healthy volunteers to confirm the involvement of an excipient, SAPP (sodium acid pyrophosphate), and the mechanism of interaction, altered gastrointestinal transit. The first study (n = 12) involved single-dose crossover comparisons of (A) 150 mg ranitidine with 1132 mg SAPP versus (B) 150 mg ranitidine and (C) 150 mg ranitidine with all the effervescent tablet excipients except SAPP versus (D) a 150-mg ranitidine effervescent tablet, all administered as oral solutions. Serum ranitidine AUC, C max, and t max were compared using two one-sided t test 90% confidence intervals (CI). Comparing treatments A to B and D to C, all 90% CI were below the 80–120% range, indicating significantly less extensive ranitidine absorption (54% based on AUC) from the oral solutions containing SAPP. The second study (n = 12) was a single-dose crossover comparing 50 µCi 111InCl solutions with and without 1132 mg SAPP. Gastrointestinal transit times, determined by scintigraphic imaging, were compared between treatments. Gastric emptying time was unchanged, but small intestinal transit time was decreased to 56% in the presence of SAPP. More rapid small intestinal transit associated with an excipient of a solution dosage form apparently resulted in a decreased extent of ranitidine absorption. This observation contradicts the conventional wisdom that oral solutions are unlikely to fall short of bioequivalence relative to solid oral formulations.
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  • 42
    ISSN: 1573-904X
    Schlagwort(e): didanosine ; pentagastrin-pretreated dog ; formulation development ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Didanosine is a purine nucleoside analogue approved for the treatment of human immunodeficiency virus infection. It is extremely unstable at pH values less than 3 and requires protection against gastric acid-induced hydrolysis. Beagle dogs pretreated with pentagastrin, an analogue of gastrin that reproducibly stimulates gastric acid secretion, have been used to screen different didanosine formulations. The absolute bioavailability of didanosine from a saline solution decreased from approximately 43% in untreated dogs to 8% after pretreatment with pentagastrin. Administration of buffered solution of didanosine to untreated and pretreated dogs yielded bio-availability estimates of 37 and 30%, respectively. In humans, the bioavailability from a similar buffered solution was approximately 40%. Pentagastrin-pretreated dogs were used to evaluate four new products relative to a citrate-phosphate buffer sachet, the formulation selected for large-scale clinical trials in humans. Two of these new formulations, a chewable tablet and an antacid suspension, were more bioavailable then the reference sachet. This also proved to be true in man, necessitating an adjustment in the dose of didanosine when administered as the chewable tablet. Dogs pretreated with pentagastrin accurately predicted the improved bioavailability of new didanosine formulations prior to clinical use. This animal model may be helpful in evaluating the biopharmaceutics of other acid-labile drugs.
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  • 43
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 10 (1993), S. 1321-1325 
    ISSN: 1573-904X
    Schlagwort(e): floating ; controlled release ; theophylline ; gastric retention time ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A novel floating controlled-release drug delivery system was formulated in an effort increase the gastric retention time of the dosage form and to control drug release. The buoyancy was attributed to air and oil entrapped in the agar gel network. A floating controlled-release 300-mg theophylline tablet having a density of 0.67 was prepared and compared in vitro and in vivo to Theo-dur. The in vitro release rate of the floating tablet was slower. In vivo scintigraphic studies for a floating and a heavy nonfloating tablet, under fasting and nonfasting conditions, showed that the presence of food significantly increased the gastric retention time for both tablets, and tablet density did not appear to make a difference in the gastric retention time. However, the positions of the floating and nonfloating tablets in the stomach were very different. Bioavailability studies in human volunteers under both fasting and nonfasting conditions showed results comparable to those with Theo-dur. The floating controlled-release theophylline tablet maintained constant theophylline levels of about 2 mg/mL for 24 hr, which may be attributable to the release from the agar gel matrix and the buoyancy of the tablet in the stomach.
    Materialart: Digitale Medien
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 41-58 
    ISSN: 1573-8744
    Schlagwort(e): transepidermal ; pharmacokinetics ; bioavailability ; drug surveillance ; compliance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Continuous transepidermal drug collection (CTDC) has been proposed for use in assessing ethanol intake and in monitoring compliance with therapeutic regimens. Exploration of a theoretical basis for use of CTDC in these circumstances and for its use in assessing other aspects of drug disposition kinetics was undertaken. Effects of single and multicompartmental drug disposition models, single dose and multiple dose regimens, with regular and irregular doses and dosing intervals, and zero-order, first-order, and Michaelis-Menten excretion patterns were explored. First-order transepidermal drug transfer was assumed with and without back transfer from the collection device. These analyses suggest that the utility of CTDC is severely restricted when back transfer from the collection device is substantial. With back transfer minimized, CTDC may be a useful tool for assessing amount of drug exposure, compliance with therapeutic regimens, and relative bioavailability, but offers little advantage over discrete sampling of other body fluids in the study of other aspects of drug disposition kinetics.
    Materialart: Digitale Medien
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 389-417 
    ISSN: 1573-8744
    Schlagwort(e): Prednisone ; prednisolone ; dose-dependent ; pharmacokinetics ; biotransformation ; protein binding ; bioavailability ; transcortin binding ; interconversion ; renal clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Six healthy male volunteers were given 5, 20, and 50 mg of oral prednisone and 5, 20, and 40 mg doses of intravenous prednisolone. Plasma and urine concentrations of prednisone and prednisolone were determined by HPLC, and the binding of prednisolone to plasma proteins was measured by radioisotopic and equilibrium dialysis techniques. The pharmacokinetics of both oral prednisone and intravenous prednisolone were dose-dependent. The mean oral dose plasma clearances of prednisone ranged from 572 ml/min/ 1.73 m 2 for the 5mg dose to 2271 ml/min/1.73 m 2 for the 50 mg dose. Changes in prednisone half-life were insignificant, but increases in the half-life of its metabolite were dose-dependent. The systemic plasma clearance of i.v. prednisolone was dose-dependent and increased from 111 to 194 ml/min/1.73 m 2 over the 5 to 40 mg i.v. dosage range. The steady-state volume of distribution also increased, but little change in mean transit time and half-life was found. The binding of prednisolone to plasma proteins was markedly concentration-dependent, and a two compartment, nonlinear equation was used to characterize the effective binding of prednisolone to transcortin and albumin. The apparent pharmacokinetic parameters of protein-free and transcortin-free prednisolone were relatively constant with dose. The interconversion of prednisone and prednisolone varied with time and dose, although prednisolone concentrations dominated by 4-to 10-fold over prednisone. In urine, 2–5% of either administered drug was excreted as prednisone and 11–24% as prednisolone. The apparent renal clearances of both steroids were also nonlinear and unrelated to protein binding. These studies indicate that the pharmacokinetics of prednisone and prednisolone are dose-dependent and that protein binding does not fully explain their apparent nonlinear distribution and disposition.
    Materialart: Digitale Medien
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 535-551 
    ISSN: 1573-8744
    Schlagwort(e): sisomicin ; pharmacokinetics ; bioavailability ; two-compartment open model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Detailed analyses of the pharmacokinetics of sisomicin administered at doses of 25, 50, and 100 mg intravenously and intramuscularly to healthy volunteers established that the drug is handled by a two-compartment open model system with a disposition (elimination) half-life of 2.6 hr. The kinetic estimates over this dose range are linear and independent of dose and were verified by a 60-min infusion experiment in which dose and the maximum serum concentration achieved (5 μg/ml) were predicted correctly. Sisomicin was rapidly distributed to the tissue compartment, and equilibrium between the central and the tissue compartment was established by 30 min after dosing. Renal clearance (55 ml/min) of sisomicin was about 30% less than total body clearance (78 ml/min). Total urinary excretion of sisomicin during a 24-hr period following drug administration was about 70% of the dose. The disposition kinetics of sisomicin following intramuscular administration are similar to those obtained following rapid intravenous administration. Intramuscular bioavailability of sisomicin for the doses of 25, 50, and 100 mg was greater than 95%. Based on these results, various initial loading infusion doses and maintenance infusion rates were calculated to provide specific desired peak and steady-state serum sisomicin concentrations rapidly. The purpose was not to expose patients to potentially toxic high peak concentrations of drug while maintaining these concentrations during the current therapeutic dosing intervals of 8 to 12 hr.
    Materialart: Digitale Medien
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 679-691 
    ISSN: 1573-8744
    Schlagwort(e): diazepam ; controlled release ; bioavailability ; single dose ; steady-state
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract A controlled release formulation of diazepam was compared to equal daily doses of the trade tablet under single day and steadystate conditions. Virtually no differences were found in the mean steadystate concentrations of diazepam or its metabolite, N-desmethyldiazepam, when the subjects received the 5 mg trade tablet three times daily or the 15 mg controlled release formulation once daily. Similarly, there was no difference in mean diazepam or N-desmethyldiazepam plasma concentrations when single doses of the controlled release formulation were given to fed or fasted volunteers. These data indicate that the controlled release formulation produces plasma concentrations of diazepam and N-desmethyldiazepam comparable to those achieved with the same daily dose of the trade product given three times daily, suggesting that these regimens can be used interchangeably.
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  • 48
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 725-738 
    ISSN: 1573-8744
    Schlagwort(e): pharmacokinetics ; chlorpheniramine ; first-pass effect ; bioavailability ; gut metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The oral absolute bioavailabilities of chloropheniramine (CPM) in four rabbits (New Zealand White, male, mean wt. 3.71 kg), averaged 0.06±0.03, 0.11±0.08, and 0.09±0.01 following a 3, 10.5, and 21 mg/kg dose, respectively. The individual bioavailability data and the AUCof one of the demethylated metabolites, desdimethyl CPM (DDCPM) obtained following different doses suggested the existence of saturable presystemic elimination. Two rabbits received an additional 10.5 mg/kg dose of CPM through portal vein infusion. Based on the oral, intraportal vein and i.v. studies, the mean extraction ratios of gut and the liver calculated for these two rabbits averaged 0.58 and 0.76, respectively. The latter value agreed well with the estimated hepatic extraction ratio from the in vitro liver homogenate study (0.89) or from the i.v. studies (0.83). The extensive prehepatic first-pass effect observed in the present study was consistent with similar findings in humans and dogs.
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 1-14 
    ISSN: 1573-8744
    Schlagwort(e): prednisone ; prednisolone ; dexamethasone ; pharmacokinetics ; tobacco ; smoking ; bioavailability ; corticosteroids ; enzyme induction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The pharmacokinetics of oral prednisone and oral dexamethasone were examined in 18 healthy male adults. Eight subjects also received intravenous prednisolone and intravenous dexamethasone. Half of each group were cigarette smokers as confirmed by plasma thiocyanate concentrations. Plasma and urine concentrations of prednisone and prednisolone were assayed by high performance liquid chromatography, while plasma dexamethasone was measured by radioimmunoassay. There were no statistically significant differences between smokers and nonsmokers in the systemic availability of prednisolone (75 versus 84%), oral dose clearance of prednisone (29 versus 27 ml/min/kg), systemic prednisolone clearance (2.8 versus 2.9 ml/min/kg), or in the interconversion rates, volumes of distribution, or urinary recoveries of prednisone and prednisolone. Similarly, the pharmacokinetics of dexamethasone were unaffected by smoking. A limited correlation (r=0.55) was found between the high oral dose clearances of prednisone and the lower values of dexamethasone (6.73 and 5.71 ml/min/kg in smokers and nonsmokers). A two- to threefold variability occurred in oral dose clearances of each steroid with partial intrasubject covariance. Unlike the anticonvulsants, which markedly induce corticosteroid metabolism, smoking has no effect on their pharmacokinetics and should not complicate therapy with these drugs.
    Materialart: Digitale Medien
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    Plant and soil 154 (1993), S. 189-196 
    ISSN: 1573-5036
    Schlagwort(e): bioavailability ; maize ; myo-inositol ; phosphorus ; phytase ; phytin ; soil
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract The effect of adding phytase to the root medium of maize plants on the P-availability of added myo-inositol hexaphosphate (phytin) has been studied in pot experiments. When 40 mM phytin-P in nutrient solution was incubated in quartz-sand for 15 days in the absence of plants, 80% of it could be recovered from the solution as soluble organic P. Maize plants growing on this mixture assimilated P from phytin at rates comparable to those from inorganic phosphate (Pi). At a lower addition rate (2 mM phytin-P) only 10% was recovered in the soil solution, and plant growth was severely limited by P. At this low phytin level, the addition of phytase (10 enzyme units per kg sand) increased the plants' dry weight yield by 32%. The relative increases of the Pi concentration in the solution and of the amount of P in the plants were even higher, indicating that the observed growth stimulation was due to an increased rate of phytin hydrolysis. The enzyme-induced growth stimulation was also observed with plants growing in pots filled with soil low in P, when phytin was added. However, on three different soils the addition rates of phytin and phytase necessary for obtaining a significant phytase effect were both about 10 times higher than those required in quartzsand. It is concluded that the P-availability from organic sources can be limited by the rate of their hydrolytic cleavage.
    Materialart: Digitale Medien
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    Hydrobiologia 253 (1993), S. 151-163 
    ISSN: 1573-5117
    Schlagwort(e): Wadden Sea ; sediments ; phosphorus compounds ; bioavailability ; algae ; iron ; calcium redox potential ; oxygen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract The purpose of this study was to make a prognosis of the effects of extended purification of terrestrial waste water, reaching the Wadden Sea by the River Rhine and Lake IJssel, on the phosphate concentration in the western Wadden Sea. The quantities of different phosphorus fractions in intertidal and subtidal sediments of the Marsdiep tidal basin (western Dutch Wadden Sea) were measured. Different methods are applied to determine the amount of phosphorus that can be released from these sediments. The direct bioavailability is determined by inoculating sediment suspensions with a natural mixture of precultured micro-organisms from the sampling area. A second approach is the measurement of the phosphate release under different redox conditions. Sequential extraction of sediment samples with different solvents is also applied. Under the present conditions and compared to the nutrient loads from fresh water (Lake IJssel) and from the North Sea, the phosphorus stored in the sediments of the western Dutch Wadden Sea plays a minor role in the total supply to micro-algae and bacteria. The bulk of the biologically available phosphorus in the sediments originates from the metal-associated fraction. Releasable phosphate may contribute to the local annual primary production to an extent of ca 45 to ca 150 g C m−2 a−1. The total amount of phosphorus in the sediment (mainly calcite associated) is twice to 6 times the biologically available amount.
    Materialart: Digitale Medien
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  • 52
    ISSN: 1573-5117
    Schlagwort(e): acid volatile sulfide ; metal ; bioavailability ; sediment ; freshwater ; temperature ; seasonal
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Acid volatile sulfide (AVS) is a natural agent in sediments which complexes some cationic metals and thereby influences the toxicity of these metals to benthic organisms. Because of its influence on metal bioavailability, AVS has been proposed as a key normalization phase for the development of sediment quality criteria for metals. However, studies conducted primarily in marine and estuarine systems have shown that AVS concentrations can vary markedly both temporally and with (sediment) depth. In this study, AVS concentrations were measured monthly for 16 mo in several segments of sediment cores from three freshwater lakes: Caribou Lake, Fish Lake and Pike Lake in northeastern Minnesota, USA. The concentrations of AVS in cores from the three lakes varied inversely with sediment depth. AVS concentrations also varied seasonally by as much as two orders of magnitude and were directly correlated with changes in water temperature. The correlation between AVS and temperature likely was related both to changes in primary productivity and sediment microbial activity.
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  • 53
    ISSN: 1572-9729
    Schlagwort(e): bioavailability ; bioluminescence ; gene probe ; in situ microbial analysis ; mRNA ; polynuclear aromatic hydrocarbons
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Energietechnik , Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Notizen: Abstract Traditional methods for quantifying specific catabolic bacterial populations underestimate the true population count due to the limitations of the necessary laboratory cultivation methods. Likewise,in situ activity is also difficult to assess in the laboratory without altering the sample environment. To circumvent these problems and achieve a truein situ bacterial population count and activity measurement, new methods based on molecular biological analysis of bacterial nucleic acids were applied to soils heavily contaminated with polycyclic aromatic hydrocarbons (PAH). In addition, a naphthalene-lux reporter system was used to determine bioavailability of naphthalene within these soils. DNA extracted from seven PAH-contaminated soils and hybridized with thenahA gene probe indicated that the naphthalene degradative genes were present in all samples in the range of 0.06 to 0.95 ng/100 µl DNA extract which was calculated to represent 3.2×106 to 1.1×1010 cells/g soil (assuming one copy of these genes per cell).14C-naphthalene mineralization was observed in all contaminated soils with14CO2 mineralization rates ranging from 3.2×10−5 to 304,920.0×10−5 µg g soil−1h−1. Phenanthrene, anthracene, and benzo(a)pyrene were mineralized also in several soils. Messenger RNA transcripts ofnahA were isolated and quantified from 4 soils. Only one soil tested, soil B, was inducible with salicylate above thein situ nahA gene transcript level. Two of the soils, C and G, were already fully inducedin situ. The naphthalene mineralization rate correlated positively with the amount ofnahA gene transcripts present (r=0.99). Naphthalene was bioavailable in soils A, D, E, G, and N as determined by a bioluminescent response from the naphthalene-lux reporter system. Taken together, these data provided information on what the naphthalene-degrading bacterial population was experiencingin situ and what approaches would be necessary to increase activity.
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  • 54
    ISSN: 1573-904X
    Schlagwort(e): pharmacokinetics ; oral absorption ; intestinal permeability ; bioavailability ; double-peaks ; dose dependency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The gastrointestinal absorption characteristics of pafenolol following oral administration as a solution in man and rat has previously been found to be a double-peak phenomenon and exhibited dose-dependent bioavailability, despite negligible presystemic metabolism. In both man and rat the first peak appeared approximately 0.5–1 hr postdose and the second, more pronounced peak 3–4 hr postdose. In rat more than 90% of the available dose was absorbed during the second peak. In the present study we investigated the absorption of a solution of pafenolol in rats after intrajejunal and intraileal administration. The resulting blood concentration–time profile of pafenolol exhibited one peak only; the extent of absorption was similar to that observed when the same dose was given orally. The small intestinal transit time of the 14C-PEG 4000 solution was found to be more than 3 hr. The transit rate was higher in the proximal part of the small intestine compared to the more distal part, where the transit of the solution was staggered. In conclusion, the results of the intestinal transit time investigation and the administrations of pafenolol at different levels of the alimentary tract indicate that pafenolol is a drug with a specific absorption site located in the ileocolonic region.
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  • 55
    ISSN: 1573-904X
    Schlagwort(e): controlled-release theophylline ; pH-dependent dissolution ; achlorhydric humans ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The bioavailability of three marketed controlled-release dosage forms and a reference solution of theophylline was studied in eight subjects with normal gastric fluid acidity and seven subjects who were achlorhydric. Gastric pH was monitored with a Heidelberg capsule. One of the controlled-release dosage forms dissolved more rapidly in vitro when exposed to acid conditions, one dissolved more rapidly in pH 7.5 media, and the third dissolved at a rate independent of pH. Using a crossover design, each subject received each dosage form twice. Blood was sampled for up to 47 hr after each dose, and serum was assayed for theophylline by HPLC. The product which dissolved more rapidly under acid conditions in vitro exhibited a 3 hr longer T max in the achlorhydrics compared to the normal subjects. The product which dissolved more rapidly in the pH 7.5 media exhibited a relatively higher AUC(0–∞) in the achlorhydric subjects than in normal subjects after the AUC data were normalized for clearance differences between the two subject groups. The in vivo bioavailability of these dosage forms could be related to the in vitro dissolution characteristics for some parameters. However, with the exception of the mean T max values, the mean bioavailability parameters differed by less than 20% between the two subject groups.
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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 10 (1993), S. 1083-1086 
    ISSN: 1573-904X
    Schlagwort(e): kappa agonist analgesic ; nasal absorption ; bioavailability ; pharmacokinetics ; ED50.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
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  • 57
    ISSN: 1573-904X
    Schlagwort(e): nonhardened gelatin–acacia microcapsules ; complex coacervation ; bioavailability ; lipophilic drugs ; O/W emulsions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Nonhardened gelatin-acacia microcapsules were studied for encapsulation of microdroplets of oil solution containing a lipophilic drug as core material and ready disintegration with release of micro oil droplets in the gastrointestinal tract. Probucol and S-312-d, a Ca-channel blocker, were employed as model lipophilic drugs. Glyceryl tricaprylate and tricaprate mixture solutions containing these drugs were encapsulated according to the complex coacervation method and were recovered as free-flowing powders without any hardening (cross-linking) step. The microcapsules obtained were disintegrated, and the emulsion was reproduced within 3 min at 37°C in the first or second test solution defined in the Japanese Pharmacopeia XII. When the microcapsules were stored as a powder at room temperature in a closed bottle, no significant change in their appearance or disintegration time upon rehydration was observed even after 1 year. Oral bioavailabilities of model drugs from the microcapsules were tested in rats and dogs and compared with those from other conventional formulations. Gastrointestinal absorption of both probucol and S-312-d from the microcapsules was remarkably more efficient than that from other formulations such as powders, granules, or oil solution. The proposed method for microencapsulation could be useful for powdering drug-containing oil solutions or O/W emulsions while maintaining excellent bioavailability.
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  • 58
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 10 (1993), S. 1191-1199 
    ISSN: 1573-904X
    Schlagwort(e): indomethacin ; naproxen ; prodrugs ; hydrolysis kinetics ; solubility ; partition coefficient ; ulcerogenicity ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Morpholinoalkyl esters (HC1 salts) of naproxen 1 and indomethacin 3 were synthesized and evaluated in vitro and in vivo for their potential use as prodrugs for oral delivery. Prodrugs were freely soluble in simulated gastric fluid (SGF) and pH 7.4 phosphate buffer and showed a minimum of a 2000-fold increase in solubility over the parent drugs. All prodrugs were more lipophilic than parent drugs as indicated by n-octanol/pH 7.4 buffer partition coefficients but less lipophilic in terms of n-octanol/SGF partition coefficients. Potentiometrically determined pK a's for prodrugs were in the range of 6.89 to 8.62 at 25°C. All prodrugs were quantitatively hydrolyzed to their respective parent drugs by enzymatic and/or by chemical means. An increase in carbon chain length rendered the prodrugs more stable at pH 7.4 but less stable in SGF. The esters were generally found to be hydrolyzed rapidly in rat plasma at 37°C, the half-lives being in the range of 1.2–31.0 min. Based on in vitro results, prodrugs 2c and 4c were chosen to evaluate solid-state stability, in vivo bioavailability, and ulcerogenicity. At elevated temperatures, the solid-state decomposition of 2c and 4c followed biphasic kinetics, with rapid decomposition occurring initially. The prodrugs were 30–36% more bioavailable orally than the parent drugs following a single equimolar solution dose in rats. Prodrugs 2c and 4c were significantly less irritating to gastric mucosa than parent drugs following single-dose and chronic oral administration in rats.
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  • 59
    ISSN: 1573-904X
    Schlagwort(e): dissolution ; bioavailability ; etodolac capsules ; stressed conditions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The dissolution and bioavailability of etodolac from capsules exposed to high relative humidity and temperature were compared to those from capsules stored at room temperature (RT). Dissolution of stressed and control capsules was evaluated using a USP basket apparatus at 100 rpm with 900 mL pH 7.5 phosphate buffer (0.05 M) at 37°C. The dissolution of etodolac from capsules exposed to stressed conditions was also evaluated with enzymes (pancreatin, 1%, w/v) added to the dissolution medium. The bioavailability of etodolac from capsules exposed to stressed conditions was compared in both dogs and humans to capsules stored at RT conditions. Capsules, 200 and 300 mg, exposed to stressed conditions failed the dissolution (without enzymes) specification [not less than 85% released (80% Q) in 30 min]. However, upon enzyme addition, all capsules met the specification. The rate and extent of absorption from these 200 and 300 mg etodolac capsules in dogs were equivalent to those from capsules stored at RT conditions that passed the dissolution specification. Similarly, the bioavailability of etodolac from 300 mg capsules that failed the dissolution specification upon exposure to stressed conditions was equivalent to that of control capsules in 24 adult male volunteers. Thus, an in vitro dissolution test with enzymes provides a better indication of stressed capsule performance in vivo.
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  • 60
    ISSN: 1573-904X
    Schlagwort(e): granulocyte colony-stimulating factor (rhG-CSF) ; recombinant human granulocyte-CSF ; nasal absorption in rats ; bioavailability ; leukocyte number
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was examined in the rat. The relative bioavailability of rhG-CSF for subcutaneous administration was ∼2%, as evaluated from the immunologically active rhG-CSF concentration in rat plasma and the area under the curve (AUC) of the plasma rhG-CSF concentration versus time for 8 hr. Pharmacological availability relative to subcutaneous administration was determined from the increase in total blood leukocyte numbers. The pharmacological availability was 5–10%, determined from the AUC for the increased ratio of total leukocyte numbers versus time for 48 hr; it was slightly dependent on the pH and the osmotic pressure of the dosing solution. Accordingly, the plasma concentration of rhG-CSF did not always reflect its pharmacological effects. Relative bioavailability and pharmacological availability were increased about 23 times and 3 times, respectively, by polyoxyethylene 9-lauryl ether (Laureth-9), but no increase in availability occurred with sodium glycocholate. The increase in total leukocyte numbers was maintained during multiple rhG-CSF dosing, and the addition of Laureth-9 further increased the pharmacological effects of this agent. This study indicates that nasal administration of rhG-CSF is an effective parenteral administration route.
    Materialart: Digitale Medien
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