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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 29 (1986), S. 555-560 
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; penbutolol ; pharmacokinetics ; drug metabolism ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A possible interaction of penbutolol and cimetidine was investigated in healthy volunteers treated orally for 7 days. The plasma levels of unmetabolised penbutolol showed a slight but non-significant increase. The biphasic elimination kinetics of penbutolol (half-lives 0.8 and 17 h) was not affected by coadministration of cimetidine. Plasma levels of penbutolol were not significantly altered by chronic treatment with cimetidine, whereas the levels of 4-hydroxypenbutolol and 4-hydroxypenbutolol glucuronide were significantly reduced.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 661-665 
    ISSN: 1432-1041
    Schlagwort(e): hydrochlorothiazide ; pharmacokinetics ; renal failure ; dosage adjustment ; excretory mechanism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of hydrochlorothiazide (HCT) was investigated in 23 subjects with normal renal function or widely varying degrees of renal failure. The half-life of elimination increased from 6.4 h in subjects with normal renal function to 11.5 h in patients with mild renal impairment (endogenous creatinine clearance between 30 and 90 ml/min), and to 20.7 h in patients with an endogenous creatinine clearance below 30 ml/min. The cumulative urinary excretion and the renal HCT clearance were correspondingly reduced in patients with impaired kidney function. In normal subjects HCT was mainly excreted by tubular secretion, but as renal HCT clearance in patients with renal impairment did not differ significantly from endogenous creatinine clearance, it was concluded that the secretory mechanism is most markedly impaired. In patients with an endogenous creatinine clearance of 30 to 90 ml/min, the dosage of HCT should be reduced to 1/2 and in patients with a endogenous creatinine clearance below 30 ml/min to 1/4 of the normal daily dose to avoid dose dependant side-effects.
    Materialart: Digitale Medien
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 29 (1985), S. 461-465 
    ISSN: 1432-1041
    Schlagwort(e): carteolol ; chronic renal failure ; pharmacokinetics ; dosage adjustment ; metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma levels and urinary excretion of carteolol and its main metabolites 8-hydroxycarteolol and carteolol glucuronide were investigated in 6 healthy subjects and 9 patients with varying degrees of renal impairment following a single oral dose of 30 mg carteolol hydrochloride. In healthy subjects the half-life of carteolol was 7.1 h. 63% of the administered dose was recovered unchanged in urine, and in all 84% was excreted by the kidneys. The renal clearance of carteolol was 255 ml/min. In chronic renal failure (CRF) the terminal half-life was increased to a maximum of 41 h. Both the elimination rate constant and renal clearance were closely related to the creatinine clearance. In CRF the recovery of carteolol and its metabolites from urine was considerably reduced, suggesting that another pathway of drug elimination becomes relevant in renal disease. To avoid an increase in side-effects due to drug accumulation, the dosage of carteolol should be adjusted in relation to the reduction in creatinine clearance. The maintenance dose should be reduced to a half in patients with a creatinine clearance below 40 ml/min and above 10 ml/min. In those with a creatinine clearance of 10 ml/min or less, the dose should be reduced to 1/4.
    Materialart: Digitale Medien
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 32 (1987), S. 303-307 
    ISSN: 1432-1041
    Schlagwort(e): azapropazone ; arthritis ; pharmacokinetics ; synovial fluid level ; synovial tissue level
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The concentration-time curves of azapropazone in synovial fluid and tissues have been studied in arthritic patients after an i.v. bolus (600 mg) and under steady-state conditions. Synovial fluid and tissue samples were taken intraoperatively 0.45–60 h after administration. The azapropazone concentrations in synovial fluid, synovial tissue and plasma were correlated. The levels in synovial fluid were usually lower than corresponding plasma levels. Under steady-state conditions azapropazone did not accumulate in synovial tissues.
    Materialart: Digitale Medien
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1982), S. 315-323 
    ISSN: 1432-1041
    Schlagwort(e): bendroflumethiazide ; propranolol ; hydralazine ; pharmacokinetics ; thin-layer chromatography ; fluorimetry ; fixed combination product
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Bendroflumethiazide (Bft) was administered to 6 healthy subjects at 3 different dose levels (2.5, 5 and 10 mg) in a cross-over design, either as capsules (2.5 mg) or as tablets (5 mg). Its pharmacokinetics were evaluated then and following administration of a fixed combination of Bft with propranolol and hydralazine to a further 7 volunteers. Plasma and urinary concentrations of Bft were determined by a new fluorimetric — thin-layer chromotography procedure. Peak plasma levels occurred after 2–3 h and averaged 15, 27 and 45 µg/l in the three dose groups. Areas under the plasma concentration — time curves (AUC0→12), which were 75, 147 and 250 µg l−1 h respectively, and cumulative urinary recovery (20%) were independent of the dose administered and the type of formulation. Thus Bft kinetics proved to be linear within the dose range evaluated. The plasma clearance was calculated to be 505 ml/min, renal clearance 108 ml/min and nonrenal clearance 396 ml/min. Bioavailability of Bft was not altered following administration of the fixed combination. The amount of propranolol found in the circulation did not change, whereas that of hydralazine (determined as apparent hydralazine) increased by 59% when the fixed combination was administered.
    Materialart: Digitale Medien
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 46 (1994), S. 537-543 
    ISSN: 1432-1041
    Schlagwort(e): Lisinopril ; Dose adjustment ; ACE inhibitors ; pharmacokinetics ; pharmacodynamics ; renal failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract To prevent drug accumulation and adverse effects the dose of hydrophilic angiotensin-converting enzyme (ACE) inhibitors, e. g. lisinopril, must be reduced in patients with renal failure. To obtain a rational basis for dose recommendations, we undertook a prospective clinical trial. After 15 days of lisinopril treatment pharmacokinetic and pharmacodynamic parameters were determined in patients with advanced renal failure (n=8; endogenous creatinine clearance [CLCR]: 18 ml·min−1·1.73m−2) and in healthy subjects with normal renal function (n=16; CLCR: 107 ml·min−1·1.73m−2). The volunteers received 10 mg lisinopril once daily, the daily dose in patients (1.1–2.2 mg) was adjusted to the individual CLCR according to the method of Dettli [13]. After 15 days of lisinopril treatment the mean maximal serum concentration (C max) in patients was lower than in volunteers (30.7 vs 40.7 ng·ml−1, while the mean area under the concentration-time curve (AUC 0–24 h) was higher (525 vs 473 ng·h−1·ml−1). ACE activity on day 15 was almost completely inhibited in both groups. Plasma renin activity, angiotensin I and angiotensin II levels documented marked inhibition of converting enzyme in volunteers and patients. Furthermore, average mean arterial blood pressure in patients decreased by 5 mmHg and proteinuria from 3.9–2.7 g per 24 h after 15 days of treatment with the reduced dose of lisinopril. Adjustment of the dose of lisinopril prevents significant accumulation of the drug in patients with advanced renal failure during chronic therapy. Mean serum levels did not exceed this in subjects with normal renal function receiving a standard dose. Despite substantial dose reduction, blood pressure and proteinuria decreases were observed.
    Materialart: Digitale Medien
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  • 17
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 49 (1996), S. 317-323 
    ISSN: 1432-1041
    Schlagwort(e): Magnesium ; Plasma level ; pharmacokinetics ; bioavailability ; circadian fluctuation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.
    Materialart: Digitale Medien
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  • 18
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 43 (1992), S. 173-177 
    ISSN: 1432-1041
    Schlagwort(e): Enalapril ; Hydrochlorothiazide ; pharmacokinetics ; renal impairment ; old patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a randomized, cross-over, single-dose study of 19 elderly hypertensive patients (aged 62–84 y, SBP 〉 160 mm Hg, DBP 〉 100 mm Hg, creatinine clearance 11–93 ml·min−1) we have studied the pharmacokinetics of the angiotensin converting enzyme (ACE) inhibitor enalapril after a single oral dose of either 10 mg enalapril or 10 mg enalapril + 25 mg hydrochlorothiazide. The pharmacokinetics of enalapril were unaffected by hydrochlorothiazide, but there was a significant reduction in renal clearance and a significant increase in AUC(0–24 h) of enalaprilat after hydrochlorothiazide, resulting in higher serum concentrations of the active drug. This was independent of the individual degree of renal impairment and might be due either to an initial reduction of GFR by hydrochlorothiazide or to interference with the tubular secretion of enalaprilat. The relationships between serum enalaprilat and serum ACE activity were similar after both treatments, both consistent with a value for Ki of enalaprilat of about 0.1 nmol·l−1. Thus, serum ACE activity was not affected by hydrochlorothiazide but completely reflected the pharmacokinetics of enalaprilat in both treatments.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 493-498 
    ISSN: 1432-1041
    Schlagwort(e): amiloride ; pharmacokinetics ; renal failure ; liver disease ; urinary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of the antikaliuretic amiloride has been studied in healthy controls and in patients with chronic renal failure or hepatitis. It was 40% bound to protein. In healthy volunteers 49% of an oral dose was recovered unchanged in the urine. The renal clearance of amiloride was about 3 times the creatinine clearance, which means that it was predominantly excreted via tubular secretion. Renal impairment reduced the clearance of amiloride, causing a prolongation of the t1/2 and drug accumulation in plasma. In hepatitis the t1/2 of amiloride was prolonged and the AUC increased. Urinary recovery (Ae) of amiloride was greater in hepatitis patients than in controls.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 20
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 38 (1990), S. 587-593 
    ISSN: 1432-1041
    Schlagwort(e): prenylamine ; racemic drug ; stereoselectivity ; metabolism ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of S-(+)- and R-(−)-prenylamine was studied in eight healthy volunteers given single and repeated oral doses of the racemic drug. Distinct differences in various pharmacokinetic parameters were found between the S- and R-enantiomer. The maximum plasma concentrations and AUCs of the R-enantiomer exceeded those of the S-enantiomer five-fold; the apparent oral clearance of the S-form was five-times and the renal clearance three-times higher than of the R-form. Acid catalyzed hydrolysis of urine samples released more S-prenylamine, indicating stereoselective glucuronidation of unchanged prenylamine. Plasma protein binding also differed between the two enantiomers, generally with a higher unbound fraction of the S-form, whereas analysis of the bound fractions showed that prenylamine was bound to different plasma proteins with inverse stereoselectivity.
    Materialart: Digitale Medien
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