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  • 1
    Electronic Resource
    Electronic Resource
    Distribution of oral ketoconazole to vaginal tissue (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 331-333 
    Details
    ISSN: 1432-1041
    Keywords: ketoconazole ; vaginal candidosis ; oral antimycotic ; distribution ; pharmacokinetics ; vaginal tissue concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma samples and biopsies of vaginal tissue were obtained from 23 healthy women undergoing operative sterilization, 1 to 6 h after a single oral dose of ketoconazole 200 mg. Drug concentrations in plasma and tissue, were measured by a specific gas chromatographic method. The vaginal tissue concentration averaged 2.4 times less than the corresponding plasma levels. Equilibrium between tissue, and plasma was established within 1 h after dosing, when vaginal tissue levels exceeded 1 µg/g. Ketoconazole concentrations decayed monoexponentially over the time interval studied (1–6 h), with the similar half-lives of 1.2 and 1.4 h in plasma and tissue, respectively. Following an oral 200 mg dose, a tissue concentration not less than 0.01 µg/ml was maintained over a 12 h period. This concentration has been shown to prevent outgrowth of the invasive (pseudo) mycelial form ofCandida albicans. Hence, a b.i.d. or t.i.d. dosage schedule of ketoconazole in vaginal candidosis would give continuously effective levels at the site of infection. Ketoconazole concentrations in vaginal fluid are thought to be much higher than in the tissue because of ion-trapping. The present data may explain the efficacy of oral ketoconazole in the treatment of vaginal candidosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613615
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  • 2
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    Sodium appetite in sheep induced by cerebral ventricular infusion of angiotensin: comparison with sodium deficiency (1981)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1981-10-09
    Description: Intraventricular administration of supraphysiological amounts of renin, nerve growth factor preparation, or angiotensin II greatly increased the consumption of water and hypertonic sodium bicarbonate solution by sheep. These effects were antagonized by intraventricular administration of drugs that prevent the formation of angiotensin II or block its receptors. The fact that these angiotensin-blocking drugs did not change the sodium intake of sodium-deficient sheep challenges the idea that central angiotensin action is involved in sodium appetite due to a deficiency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coghlan, J P -- Considine, P J -- Denton, D A -- Fei, D T -- Leksell, L G -- McKinley, M J -- Muller, A F -- Tarjan, E -- Weisinger, R S -- Bradshaw, R A -- New York, N.Y. -- Science. 1981 Oct 9;214(4517):195-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6169149" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/*pharmacology ; Animals ; Appetite/*drug effects ; Drinking Behavior/drug effects ; Injections, Intraventricular ; Nerve Growth Factors/pharmacology ; Renin/pharmacology ; Saralasin/pharmacology ; Sheep ; Sodium/deficiency/*metabolism ; Teprotide/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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    PAPER CURRENT
  • 3
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    Implications of new measurements of O-16 + p + C-12,13, N-14,15 for the abundances of C, N isotopes at the cosmic ray source (1985)
    In:  CASI
    Details
    Publication Date: 2019-06-28
    Description: The fragmentation of a 225 MeV/n O-16 beam was investigated at the Bevalac. Preliminary cross sections for mass = 13, 14, 15 fragments are used to constrain the nuclear excitation functions employed in galactic propagation calculations. Comparison to cosmic ray isotonic data at low energies shows that in the cosmic ray source C-13/C approximately 2% and N-14/0=3-6%. No source abundance of N-15 is required with the current experimental results.
    Keywords: SPACE RADIATION
    Type: OG-4.3-2 , 19th Intern. Cosmic Ray Conf - Vol. 2; p 80-83; NASA-CP-2376-VOL-2
    Format: application/pdf
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    NASA TECHNICAL REPORTS
  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of chlormethiazole in healthy volunteers and patients with cirrhosis of the liver (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 275-284 
    Details
    ISSN: 1432-1041
    Keywords: chlormethiazole ; cirrhosis of the liver ; antipyrine ; protein binding ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole after oral and intravenous administration was studied in six healthy volunteers and eight patients with alcoholic cirrhosis of the liver. Plasma concentration-time curve after the intravenous infusion could adequately be described by two- or three-compartment open models both in healthy volunteers and in the patients. Based on the areas under the plasma concentration-time curves, the systemic bioavailability of oral chlormethiazole was about ten times greater in the patients than in healthy controls. The elimination of chlormethiazole was relatively less retarded in the patients, as indicated by a decrease of about 30% in its plasma clearance. In the patients the plasma protein binding of chlormethiazole was decreased, but the volume of distribution and half-life of elimination were unchanged. The increase in bioavailability of chlormethiazole was associated with significant alteration in the serum levels of bilirubin, albumin, alkaline phosphatase, prothrombin-proconvertin activity (P + P) and elimination rate of antipyrine or14C-aminopyrine. The increased bioavailability of oral chlormethiazole was due to impaired first-pass metabolism in the cirrhotic liver. A considerable reduction in dose seems to be indicated if oral chlormethiazole is used in patients with advanced cirrhosis of the liver. A substantial fraction of dose, averaging 15%, was lost during the intravenous infusion, presumably due to adsorption to the infusion tubing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00625801
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  • 5
    Electronic Resource
    Electronic Resource
    A double-blind and cross-over comparison of once daily doxazosin and placebo with steady-state pharmacokinetics in elderly hypertensive patients (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 119-123 
    Details
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha1-adrenoceptor inhibitor ; elderly patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The α1-adrenoceptor antagonist doxazosin has been compared with placebo in 40 elderly hypertensive patients (mean age 71.4 years). At the end of 10 weeks once daily treatment with doxazosin the mean 24-h post-dose changes in standing and supine blood pressure compared with placebo were −6.9/−5.6 mmHg (systolic/diastolic) and −6.2/−5.5 mmHg respectively. The reductions in standing and supine diastolic blood pressures were statistically significant compared with placebo. At the end of treatment steady-state pharmacokinetics were evaluated in 18 patients. The plasma elimination half-life during the dose interval in these patients was 16.1 h (range 10.1–27.1 h) and the median time to peak plasma concentration was 3 h (range 1–4 h). One patient was withdrawn because of adverse effects (headache, weakness, and sweating) during doxazosin treatment. Once daily doxazosin reduced diastolic blood pressure and was well tolerated in these elderly hypertensive patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614546
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  • 6
    Electronic Resource
    Electronic Resource
    Effect of probenecid on the elimination and protein binding of ceftriaxone (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 151-156 
    Details
    ISSN: 1432-1041
    Keywords: ceftriaxone ; probenecid ; drug interaction ; protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics and binding parameters of ceftriaxone have been characterized in eight normal subjects who received, in sequence, 1.0 g ceftriaxone and 1.0 g ceftriaxone together with 250 and 500 mg probenecid q.i.d. Probenecid increased the total systemic clearance (CL S T ) from 0.244 to 0.312 ml/min/kg, whereas the terminal half-life (t 1/2(β) T ) fell from 8.1 to 6.5 h. In contrast, the renal clearance of free ceftriaxone (CL R F ) was decreased from 2.09 to 1.67 ml/min/kg, confirming a small but significant contribution of tubular secretion to the renal elimination of ceftriaxone. The final value of CL R F was attained with the lower dose probenecid, whereas the non-renal clearance of free ceftriaxone (CL NR F ) fell progressively from 2.78 to 1.90 ml/min/kg with the increasing probenecid dose. The total decrease in the systemic clearance of free ceftriaxone (CL S F ) after the higher dose of probenecid was about 30% (4.87 to 3.57 ml/min/kg). As a consequence of a decreased affinity constant (KA), the average free fraction in plasma (f) was increased by 54% after the low dose and by 74% after the high dose of probenecid. The protein binding interaction between probenecid and ceftriaxone appears to be unique. The results are of limited clinical consequence for ceftriaxone but they emphasise the importance of evaluating the kinetics of the free drug when examining interactions involving probenecid.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614552
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ipratropium bromide after single dose inhalation and oral and intravenous administration (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 189-194 
    Details
    ISSN: 1432-1041
    Keywords: ipratropium bromide ; radioceptor assay ; pharmacokinetics ; inhalation ; systemic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single doses of ipratropium bromide were administered intravenously, orally and by slow inhalation to ten healthy male volunteers. The plasma level after oral administration followed a low but broad plateau persisting for several hours. After i.v. administration the kinetic parameters were: Vc=25.9 l, Vα=13.1 l, Vβ=338 l, $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\alpha }}} \right. \kern-\nulldelimiterspace} {2_\alpha }}} = 3.85\min $$ , $$t_{{1 \mathord{\left/ {\vphantom {1 {2_\beta }}} \right. \kern-\nulldelimiterspace} {2_\beta }}} = 98.4\min $$ , AUC=15.0 h · ng/ml, kel=11.8 l/h and total clearance is 2325 ml/min. The bioavailability was 3.3% (range 0.9–6.1%) on comparing the plasma AUCs following i.v. and 20 mg oral administration. The cumulative renal excretion (0–24 h) after i.v. administration was compared with that after oral administration and inhalation. Following oral administration, the apparent systemic availability was around 2%, and after inhalation it was 6.9%. In comparison with oral placebo administration, only after i.v. administration was there a significant change in heart rate (from 63.7 to 90.2 beats/min). The systolic blood pressure rose from 115.1 to 119.6 mm Hg and the diastolic blood pressure from 68.3 to 78.3 mm Hg.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609193
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  • 8
    Electronic Resource
    Electronic Resource
    Interaction between furosemide and the converting enzyme inhibitor benazepril in healthy volunteers (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 465-468 
    Details
    ISSN: 1432-1041
    Keywords: benazepril ; furosemide ; converting enzyme inhibitor ; pharmacokinetics ; drug interaction ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of 10 mg converting enzyme inhibitor benazepril (CGS 14824A) and 40 mg furosemide were administered to 12 healthy male volunteers either separately or concomitantly. The pharmacokinetic parameters of benazepril were not influenced by coadministration of furosemide. Urinary excretion of total furosemide was significantly reduced by 10 to 20% in the presence of benazepril. This effect was considered clinically insignificant. Erect blood pressure decreased and pulse rate increased only during concomitant treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01046703
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  • 9
    Electronic Resource
    Electronic Resource
    The effects of domperidone on the absorption of levodopa in normal subjects (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 721-723 
    Details
    ISSN: 1432-1041
    Keywords: domperidone ; levodopa ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of simultaneous oral administration of 20, 40, or 80 mg domperidone on the pharmacokinetics of an oral 500 mg dose of levodopa was studied in eight normal women. No significant differences in maximum plasma levodopa concentration, the time of its attainment, or the area under the plasma levodopa concentration versus time profile occurred. Domperidone significantly reduced the incidence of adverse gastrointestinal effects due to levodopa administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00615966
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  • 10
    Electronic Resource
    Electronic Resource
    Plasma and salivary pharmacokinetics of caffeine in man (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 45-52 
    Details
    ISSN: 1432-1041
    Keywords: caffeine ; pharmacokinetics ; plasma ; saliva ; urinary elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and salivary caffeine concentrations were measured by gas-liquid chromatography in 6 healthy caffeine-free volunteers following oral administration of 50, 300, 500 and 750 mg caffeine. Caffeine was also given to a single subject intravenously in doses of 300, 500 and 750 mg. Caffeine was rapidly absorbed and was completely available at all doses. The apparent first-order elimination rate constant decreased linearly with dose and was 0.163±0.081 h−1 for 50 mg and 0.098±0.027 h−1 for 750 mg. The total body clearance was unaffected by dose and was 0.98±0.38 ml/min/kg. There was a trend towards increasing apparent volume of distribution with increasing dose. A linear relationship existed between the area under the plasma concentration, time curve and dose and dose-normalised plasma concentration, time plots were superimposable. These findings suggest that caffeine obeys linear pharmacokinetics over the dose range investigated. Despite significant inter-individual differences in pharmacokinetic parameters there was good reproducibility within 5 subjects given 300 mg caffeine orally on 3 occasions. Salivary caffeine levels probably reflect the unbound plasma caffeine concentration and can be used to estimate the pharmacokinetic parameters of the drug. Overall the saliva/plasma concentration ratio was 0.74±0.08 but within subjects some time-dependence of the ratio was found with higher ratios initially (even after intravenous administration) and lower ratios at longer time intervals after the dose. Urinary elimination of caffeine was low and independent of dose: 1.83% of the dose was eliminated unchanged.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609587
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