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  • 1
    Electronic Resource
    Electronic Resource
    Pharmakokinetik von Triamteren bei Probanden und Patienten mit Leber- und Nierenfunktionsstörungen (1983)
    Springer
    Journal of molecular medicine 61 (1983), S. 883-891 
    Details
    ISSN: 1432-1440
    Keywords: Triamterene ; Pharmacokinetics ; Metabolism ; Bioavailability ; Determination ; Liver disease ; Renal disease ; Age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The knowledge about the pharmacokinetics of triamterene (TA) was limited until recently. The metabolic pathway of TA is the formation of p-hydroxytriamterene (OH-TA), which is subsequently conjugated with active sulfate to form p-hydroxytriamterene sulfuric acid ester (OH-TA-ester). The phase-II-metabolite is surprisingly pharmacologically active. TA and its metabolites were measured concomitantly by a specific and sensitive tlc-method. The i.v. kinetics of TA were determined after application of a newly developed lactic acid solution of the drug. Comparing these data with results after oral application of TA the bioavailability of TA was 52% and the extent of absorption 83%. The bioavailability of different dosage forms was correlated with in vitrotests. In liver disease the pharmacokinetics of TA are markedly altered. While in cirrhosis the hydroxylation of TA was decreased, the biliary excretion of this agent was strongly reduced in hepatitis. In renal disease the excretion of TA and OH-TA-ester was reduced proportional to the reduction of endogenous creatinine clearance. In older patients the elimination of TA was impaired.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01537528
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  • 2
    Electronic Resource
    Electronic Resource
    Interaction of metoprolol, propranolol and atenolol with concurrent administration of cimetidine (1982)
    Springer
    Journal of molecular medicine 60 (1982), S. 1401-1407 
    Details
    ISSN: 1432-1440
    Keywords: Drug Interaction ; Cimetidine ; Metoprolol, propranolol, atenolol ; Chronic treatment ; Arzneimittelinteraktion ; Cimetidin ; Metoprolol, Propranolol, Atenolol ; Chronische Therapie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Pharmakokinetik von Metoprolol, Propranolol und Atenolol wurde nach jeweils 7tägiger oraler Monotherapie mit diesen Substanzen und nach 7tägiger kombinierter Gabe jedes Betablockers zusammen mit Cimetidin bei 6 gesunden Probanden geprüft. Cimetidinapplikation führte zu keiner Änderung des kinetischen Verhaltens von Atenolol. Demgegenüber stiegen nach Cimetidingabe die maximalen Metoprolol-Plasmaspiegel durchschnittlich um 70% und die von Propranolol um 95% im Vergleich zur Monotherapie mit diesen beiden Betablockern an (P〈0,05). Ähnlich verhielt sich die AUC beider Betablocker unter zusätzlicher Therapie von Cimetidin (P〈0,05). Bis auf einen geringen, jedoch nicht signifikanten Anstieg der Eliminationshalbwertzeit von Metoprolol und Propranolol bei gleichzeitiger Cimetidingabe wurden andere kinetische Parameter dieser beiden Pharmaka durch Cimetidin nicht bemerkenswert verändert. Die am 6. Tag jeder Behandlungsphase gemessene Hemmung der belastungsabhängigen Tachykardie ergab keine signifikanten Unterschiede zwischen der Monotherapie mit den jeweiligen Betablockern und deren kombinierter Gabe mit Cimetidin. Außer einem Probanden, der am 6. Tag der Therapie mit Metoprolol und Cimetidin über Angstgefühl, Schwäche und Schweißausbruch klagte, wurden weder in der Behandlungsperiode von Cimetidin mit den 3 Betablockern noch in den Monotherapiephasen Nebenwirkungen beobachtet.
    Notes: Summary Pharmacokinetics of metoprolol, propranolol, and atenolol were investigated in six healthy volunteers following 7 days of oral monotherapy with these drugs, and after 7 days concurrent administration of each of these betareceptor antagonists with cimetidine. Application of cimetidine did not lead to any interaction with atenolol, whereas mean peak plasma levels of metoprolol were increased by 70%, and those of propranolol by 95% due to concurrent administration of cimetidine (P〈0.05). The plasma level time curve (AUC) of the two above-mentioned beta blockers behaved similarly (P〈0.05). Other kinetic parameters of these two drugs were not influenced to a statistically significant extent by cimetidine, despite the tendency for the elimination half-life of metoprolol and propranolol to be prolonged when cimetidine is added. Measurement of exercise-induced tachycardia on the sixth day of administration showed no differences between monotherapy with the beta blockers and combined treatment with each of them together with cimetidine. Apart from one volunteer who complained of anxiety, weakness, and sweating on the sixth day of cimetidine/metoprolol administration, no adverse effects could be observed during the combination therapy with cimetidine and the beta blockers, nor during monotherapy with beta blockers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01716245
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection (1993)
    Springer
    Journal of molecular medicine 71 (1993), S. 622-627 
    Details
    ISSN: 1432-1440
    Keywords: Angiotensin-converting enzyme inhibitors ; Cilazapril ; Furosemide ; Natriuresis ; Antinatriuresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The goal of this study was to quantitate the effect of angiotensin-converting enzyme inhibition on renal sodium handling after furosemide injection. The study was carried out on low and normal salt intake to assess potential interaction with salt balance. Eighteen healthy normotensive volunteers were examined in a double placebo-controlled parallel group design. Subjects were randomly put on either low-salt (20 mmol/day) or normal-salt (110 mmol/day) diet. In either arm of the diet volunteers were first treated orally with placebo for 1 week and subsequently with 2.5 mg/day of the angiotensin-converting enzyme inhibitor cilazapril for another 1 week. Cumulative 24-h urinary sodium excretion was measured on the 6th day of the respective week after sham injection and on the 7th day after injection of 40 mg furosemide. Compared to pretreatment with placebo, pretreatment with cilazapril resulted in a higher cumulative sodium excretion after furosemide injection (day 7) than after the sham injection (day 6) on both salt intakes. The difference in natriuresis (cilazapril versus placebo) was evident 2 and 3 h after injection of furosemide. Neither the time of onset nor the magnitude of antinatriuresis were affected by cilazapril. Following furosemide angiotensin II increased significantly even after cilazapril pretreatment. Cilazapril tended to reduce urinary furosemide excretion. At any given urinary furosemide concentration, the increment in urinary sodium excretion was significantly greater with cilazapril irrespective of salt intake. The study shows that (a) cilazapril increases furosemide-induced natriuresis irrespective of salt intake, (b) antinatriuresis is not affected by cilazapril, and (c) angiotensin II levels rise after furosemide on cilazapril in therapeutic doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00184489
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  • 4
    Electronic Resource
    Electronic Resource
    Prediction of diuretic mobilization of cirrhotic ascites by pretreatment fractional sodium excretion (1990)
    Springer
    Journal of molecular medicine 68 (1990), S. 545-551 
    Details
    ISSN: 1432-1440
    Keywords: Ascites ; Liver cirrhosis ; Xipamide ; Spironolactone ; Furosemide ; Resistance to diuretics ; Fractional sodium excretion ; Side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a randomized prospective study the efficacy and side effects of xipamide versus the combination spironolactone/furosemide in the treatment of cirrhotic ascites were studied. Out of 27 patients four responded to a basic treatment consisting of salt and water restriction and one had to be excluded because of deterioration of kidney function. The remaining 22 patients were randomized to additional treatment with either 20 mg xipamide/day (group I) or 200 mg spironolactone/ day combined with 40 mg of furosemide every other day (group II). A response to treatment during the first 4 days was seen in 7 of 11 patients of group I versus only 3 of 11 patients in group II. In the latter group 7 of 11 patients finally responded after 8 days of treatment. Responsiveness to either diuretic treatment strongly depended on pretreatment fractional Na excretion, FENa. The resistance to diuretic treatment can be predicted by a FENa〈0.2%, and could be overcome by additional strategies known to reduce avid proximal Na reabsorption. Xipamide frequently induced hypokalemia, whereas hyperkalemia was seen following treatment with spironolactone/furosemide. Kidney function remained stable during either diuretic treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01667146
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  • 5
    Electronic Resource
    Electronic Resource
    Does cantharides blister fluid provide access to the peripheral compartment? (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 327-330 
    Details
    ISSN: 1432-1041
    Keywords: bendroflumethiazide ; cantharides plasters ; blister fluid ; plasma levels ; pharmacokinetics ; compartmental analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of bendroflumethiazide (BFT) was investigated following the oral administration of 10 mg to 3 healthy volunteers. Each subject participated twice in the study. BFT was determined in plasma and cantharides blister fluid from 1/2 to 30 h post administration. Blister fluid was obtained from blisters 10–22 h old. Plasma levels were fitted to a tri-exponential equation and the concentration of the drug in the peripheral compartment was calculated from the microscopic rate constants. In 5 of 6 cases investigated, cantharides blister fluid levels paralleled the concentration of the drug in the peripheral compartment. The mean blister fluid levels exceeded the calculated concentration in Compartment 2 1.46 fold. In one case, the blister fluid level paralleled the plasma level. This subject clearly differed from the others as more than 10 h were required for blister formation in her. The results suggest that following the administration of BFT, cantharides blister fluid behaves as part of the peripheral compartment. The possible value of studying blister fluid levels in pharmacokinetic investigations is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613614
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacodynamics and kinetics of etozolin/ozolinone in hypertensive patients with normal and impaired kidney function (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 687-693 
    Details
    ISSN: 1432-1041
    Keywords: etozolin ; ozolinone ; furosemide ; hypertension ; renin ; catecholamines ; chronic renal failure ; steady state kinetics ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect on urinary electrolyte excretion, renin release and plasma norepinephrine of single oral doses of 400 mg etozolin (E) and of 40 mg furosemide (F) were studied in hypertensive patients with normal (n=6) and impaired kidney function (n=6). E caused a marked saluresis up to 24 hours, showing its long duration of action. F, however, displayed a brief, brisk peak diuresis, followed by a rebound from the 4th to the 24th hours. The brisk peak diuresis induced by F was associated with pronounced release of renin, almost twice that induced by E. In chronic renal failure the renin release in relation to the magnitude of the diuresis was increased, i.e. the sensitivity of these patients to changes in water homeostasis was increased. E and F stimulated the sympathetic system to roughly the same extent. Patients with essential hypertension had higher plasma levels of norepinephrine than hypertensive patients with chronic renal failure. In addition, hypertensive patients with normal renal function (n=4) and varying degrees of renal impairment (n=11) were also given 400 mg daily for 2 weeks. Effects on blood pressure and electrolyte homeostasis were monitored, as well as the plasma kinetics of metabolite I, ozolinone. At the end of the 2 week treatment E had significantly lowered systolic (−12 mm Hg) and diastolic (−9 mm Hg) blood pressure, and had produced a significant loss of body weight, without altering plasma electrolytes or blood chemistry. There was no accumulation of the effective metabolite ozolinone under conditions of severe impairment of kidney function. It is concluded that E can effectively control high blood pressure in patients with normal and impaired kidney function. Its effective metabolite ozolinone did not accumulate in chronic renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541926
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of bendroflumethiazide alone and in combination with propranolol and hydralazine (1982)
    Springer
    European journal of clinical pharmacology 21 (1982), S. 315-323 
    Details
    ISSN: 1432-1041
    Keywords: bendroflumethiazide ; propranolol ; hydralazine ; pharmacokinetics ; thin-layer chromatography ; fluorimetry ; fixed combination product
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bendroflumethiazide (Bft) was administered to 6 healthy subjects at 3 different dose levels (2.5, 5 and 10 mg) in a cross-over design, either as capsules (2.5 mg) or as tablets (5 mg). Its pharmacokinetics were evaluated then and following administration of a fixed combination of Bft with propranolol and hydralazine to a further 7 volunteers. Plasma and urinary concentrations of Bft were determined by a new fluorimetric — thin-layer chromotography procedure. Peak plasma levels occurred after 2–3 h and averaged 15, 27 and 45 µg/l in the three dose groups. Areas under the plasma concentration — time curves (AUC0→12), which were 75, 147 and 250 µg l−1 h respectively, and cumulative urinary recovery (20%) were independent of the dose administered and the type of formulation. Thus Bft kinetics proved to be linear within the dose range evaluated. The plasma clearance was calculated to be 505 ml/min, renal clearance 108 ml/min and nonrenal clearance 396 ml/min. Bioavailability of Bft was not altered following administration of the fixed combination. The amount of propranolol found in the circulation did not change, whereas that of hydralazine (determined as apparent hydralazine) increased by 59% when the fixed combination was administered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637620
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of triamterene after i.v. administration to man: Determination of bioavailability (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 237-241 
    Details
    ISSN: 1432-1041
    Keywords: triamterene ; bioavailability ; pharmacokinetics ; metabolism ; hydroxy triamterene sulphate ; urinary excretion ; i.v. administration ; first-pass-effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. The formation of OH-TA-ester was very rapid and the concentration of the metabolite exceeded that of TA at all times. After i.v. administration the urinary recovery of TA and OH-TA-ester was 4.4% and 50.9%, respectively. The bioavailability of TA was 52%, corresponding to absorption of 83%. TA is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543797
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  • 9
    Electronic Resource
    Electronic Resource
    Plasma salicylate levels and platelet function after acute and chronic administration of slow-release acetylsalicylic acid (Monobeltin) (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 683-687 
    Details
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; slow-release-formulation ; platelet function ; plasma salicylates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relationships between the antiplatelet effects and the pharmacokinetics of a slow release formulation of acetylsalicylic acid (ASA) have been investigated. After acute intake of 750 mg ASA in a slow-release formulation (Monobeltin), a slow increase in plasma ASA was paralleled by a gradual decrease in certain platelet functions. During chronic medication (750 mg twice daily), ASA was present in plasma at all times accompanied by full inhibition of platelet aggregation. For chronic antiplatelet therapy, this slow release formulation of ASA appears to be very effective, unless rapid inhibition of platelet function must be achieved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547049
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  • 10
    Electronic Resource
    Electronic Resource
    Human plasma and skin blister fluid levels of griseofulvin following a single oral dose (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 109-113 
    Details
    ISSN: 1432-1041
    Keywords: griseofulvin ; skin blister fluid levels ; pharmacokinetics ; healthy subjects ; bioavailability ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Griseofulvin and 6-demethylgriseofulvin (6-DMG) in plasma, suction blister fluid (SBF) and cantharides blister fluid (CBF) and urinary excretion of 6-DMG, were evaluated following administration of single oral doses of an ultramicrosize and a microsize formulation of griseofulvin to 6 healthy volunteers. The bioavailability of griseofulvin was higher following the ultramicrosize formulation when 64% of the dose was recovered (via metabolites) versus 52% after the microsize preparation. Penetration into skin blister fluid was delayed as compared to plasma levels; the peak concentration in plasma was observed at 3–4 h, whereas griseofulvin in CBF increased up to 6 h. The terminal half-live was calculated from plasma levels to 9.3 h. The half-lives calculated from SBF and CBF concentrations were 9.2 and 9.8 h, respectively, (n=5). In plasma 84% of griseofulvin was bound to proteins, predominantly to albumin; binding in SBF and CBF was 72 and 82%, respectively. 3 h after drug administration the free concentration in plasma significantly exceeded the free concentrations in SBF and CBF. Distribution equilibrium between plasma and skin blister fluid was observed after 27 h. Thus, during chronic administration, the plasma griseofulvin level should reflect its concentration in the target organ.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547378
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