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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 54 (1998), S. 767-771 
    ISSN: 1432-1041
    Keywords: Key words Propiverine ; Fatty liver disease ; Pharmacokinetics ; Adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The present study was designed to assess the pharmacokinetics of propiverine after single and multiple dosing in patients with and without fatty liver disease. Methods: The serum concentration-time curves of propiverine and its main metabolite propiverine-N-oxide were investigated in 12 patients with mild to moderate impairment of liver function (mean antipyrine clearance 26.0 ml · min−1) and in 12 controls (antipyrine clearance 42.8 ml · min−1). Subjects were treated orally with propiverine hydrochloride (Mictonorm) for 5 days (15 mg t. i. d.) to reach steady state. Results: No significant differences were observed for propiverine and its main metabolite with regard to peak serum concentration (Cmax), area under the serum concentration-time curve (AUC) and elimination half-life (t1/2). Adverse events were reported by 12 patients. Five patients with fatty liver disease and seven patients with normal liver function complained of dry mouth and/or blurred vision. All adverse events reported were transient and mild. Conclusion: No pharmacokinetic differences relevant for safety were observed, comparing patients with and without fatty liver disease following repeated oral administration of propiverine. Thus there seems to be no need to adjust the dose in patients with mild to moderate impairment of liver function.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 54 (1998), S. 667-668 
    ISSN: 1432-1041
    Keywords: Key words Drug Information Centre ; Primary healthcare
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 14 (1978), S. 405-412 
    ISSN: 1432-1041
    Keywords: Colloidal plasma substitutes ; cross-linked polypeptides ; Haemaccel® ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Infusions of 3.5% isocyanate cross-linked polypeptide solution 500 ml were given to 52 patients with normal or impaired renal function: glomerular filtration rate (GFR)=0–133 ml/min. The serum concentration and urinary excretion of hydroxyproline were measured and the equivalent polypeptide concentrations were calculated from the results. In patients with normal renal function (GFR〉90 ml/min) the proportion of polypeptide excreted in the urine up to 12 h was 45.4±2.6% ( $$\bar X$$ ±SEM), up to 24 h 47.7±2.9% and up to 48 h 49.3±3.4%. In patients with moderate renal insufficiency (GFR=30–90 ml/min) there was no decrease in polypeptide excretion and even in patients with more serious impairment of GFR (11–30 ml/min) 48-h urinary polypeptide excretion was still 40.6±5.9%. In patients with GFR of 2–10 ml/min polypeptide excretion fell to 10.7±3.2% during the first 12 h, although there was an increase in later collection periods as compared to patients with normal renal function −19.9±3.9% in 24 h and 27.0±3.5% in 48 h. The elimination half-life (t1/2) calculated from serum concentrations was 505±30 min ( $$\bar X$$ ±SEM) in patients with normal renal function (GFR〉90 ml/min). Only when the GFR fell below 30 ml/min did it slowly begin to increase. In patients with minimal residual renal function (GFR=0–0.5 ml/min), who were on haemodialysis, the elimination half-life was 985±49 min, i.e. approximately twice the normal. Twice weekly infusion of 3.5% polypeptide solution 500 ml over a period of 6 weeks did not produce any significant cumulation in haemodialysis patients (GFR=0–0.5 ml/min). A weekly dose of polypeptide 35 g appeared to be quite safe when given for several weeks, even to anuric patients. As no significant amount of polypeptide was lost during haemodialysis, the dose can be chosen without taking into account any effect of intermittent haemodialysis.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 29 (1985), S. 199-206 
    ISSN: 1432-1041
    Keywords: cimetidine ; ranitidine ; liver microsomes ; enzyme inhibition and induction ; monooxygenase activity ; microsomal drug metabolism ; human liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Human hepatic microsomes were isolated from wedge biopsies of the liver from 13 patients undergoing abdominal surgery. Ultrasonic homogenisation was used to increase the yield of microsomal monooxygenase activity (7-ethoxycoumarin O-deethylase, NADPH-cytochrome c reductase), resulting in a 30% higher total enzyme activity per g liver than preparation by other techniques. In 4 individual microsomal preparations the influence of cimetidine and ranitidine on Michaelis-Menten kinetics of O-deethylation and of reductase activity were studied. Without the H2-receptor blocking drugs, enzyme kinetics of O-deethylation with a Km of 51.0±16.4 µM (n=3) were obtained using Lineweaver-Burke plots. Both, cimetidine and ranitidine inhibited the O-deethylation; cimetidine had a five-fold higher inhibitory affinity (Ki 1.01 and 3.94 mM) to the monooxygenase than ranitidine (Ki 4.96 and 17.70 mM) in the uninduced liver. However, in liver from a patient with induced enzyme activity (Km=478.0 µM), the Ki of ranitidine was similar to that of cimetidine (Ki ran 3.57 versus Ki cim 2.49 mM). The reductase activity was not inhibited by ranitidine and only marginally so by cimetidine. The results suggest that in human hepatic microsomes oxidative drug metabolism is inhibited by both H2-receptor antagonists. However, the inhibitory potency of the compounds seems to depend on the individual isozyme pattern of the hepatic microsomes. Thus, while cimetidine is an relatively nonspecific enzyme inhibitor, ranitidine might more selectively inhibit induced drug metabolizing enzymes.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 433-437 
    ISSN: 1432-1041
    Keywords: nitrendipine ; renal failure ; haemodynamic effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In sixteen patients with arterial hypertension and differing degrees of renal function the pharmacokinetics and haemodynamic effects of nitrendipine have been studied after treatment for 7 days. The AUC (0–24) and the elimination half-life of nitrendipine were significantly increased; the AUC (0–24) in patients with renal failure (median creatinine clearance 27.1 ml × min−1) was 196 ng × ml−1 × h compared to 97.8 ng × ml−1 × h in control subjects (median creatinine clearance 94.4 ml × min−1). The corresponding elimination half-lives were 13.5 h in renal failure and 4.4 h in the controls. The haemodynamic effects of nitrendipine were not enhanced in the patients.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 54 (1998), S. 35-39 
    ISSN: 1432-1041
    Keywords: Key words Amrinone ; Enoximone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To compare the venodilator potencies of the phosphodiesterase (PDE) III inhibitors amrinone and enoximone with the unspecific PDE inhibitors theophylline and pentoxifylline in human hand veins in vivo. Methods: Eighteen healthy nonsmokers (16 men and two women) were studied using the dorsal hand vein technique. After preconstriction with the selective α1-adrenergic-receptor agonist phenylephrine dose–response curves were constructed for amrinone (1–270 μg · min−1), enoximone (1–270 μg · min−1), theophylline (5–1500 μg · min−1) and pentoxifylline (2–877 μg · min−1) in a random order on separate occasions. Due to limitation in the maximum dose infused in order to avoid systemic effects, full dose–response curves could not be constructed for pentoxifylline. In this case, the individual dose of pentoxifylline and theophylline producing 50% venodilation were compared. Results: All PDE inhibitors induced dose-dependent venodilation. The value of maximum venodilation was the same for amrinone, enoximone and theophylline. The infusion rate needed to induce 50% of maximum venodilation (ED50) was not significantly different for amrinone (geometric mean, 8.8 μg · min−1) and enoximone (14.2 μg · min−1), whereas the ED50 of theophylline (84.0 μg · min−1) was significantly higher than either amrinone or enoximone. The dose necessary to dilate the vein to 50% the maximum dilation (as determined during sodium chloride infusion) was significantly higher for pentoxifylline than for theophylline (409 vs 71 μg · min−1). Conclusions: These findings demonstrate that enoximone and amrinone have similar venodilatory potency which is six times higher than that of theophylline. The least potent vasodilator in this study was pentoxifylline.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 19 (1981), S. 65-71 
    ISSN: 1432-1041
    Keywords: atenolol ; haemodialysis ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of atenolol were determined following acute intravenous and chronic oral administration to 20 subjects with a glomerular filtration rate (GFR) between 5 and 113 ml/min. Plasma levels in a further 5 patients on haemodialysis were measured after intravenous treatment. The mean half life of elimination increased from 5.9 h in patients with normal renal function to 42.1 h in preuraemic patients (GFR 〈10 ml/min) following a single i. v. dose. The half life of elimination following chronic oral administration was not significantly different. Mean peak plasma concentrations increased from 540 ng/ml in patients with normal renal function to 1493 ng/ml in preuraemic patients following chronic oral treatment with 100 mg/day. The mean half life of elimination during a single haemodialysis treatment was 4.3 h. In patients with a GFR 〉30 ml/min the normal daily dose of atenolol should be employed, in patients with a GFR between 10 and 30 ml/min the dose should be reduced by half, and in patients with a GFR 〈10 ml/min a reduction by three quarters of the normal dose is recommended.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 109-110 
    ISSN: 1432-1041
    Keywords: bisoprolol ; cimetidine ; interaction ; renal clearance ; tubular secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 261-265 
    ISSN: 1432-1041
    Keywords: Frusemide ; probenecid ; phenprocoumon ; anticoagulant ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of phenprocoumon with and without co-administration of frusemide and probenecid in two groups of 17 healthy volunteers. Frusemide 40 mg b.i.d. for 7 days did not interact with phenprocoumon to a significant extent. Probenecid 500 mg q.i.d. for 7 days significantly accelerated the overall elimination of phenprocoumon, as indicated by a decrease in AUC from 295 to 157 μg · h · ml−1, and a reduction in the fraction of the dose excreted by the kidneys. The data are consistent with inhibition of the glucronidation of phenprocoumon by probenecid. Its accelerated elimination may be a consequence of the increased formation of hydroxylated metabolites.
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  • 10
    ISSN: 1432-1041
    Keywords: Nitrendipine ; enantiomers ; stereoselectivity ; Renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the enantiomers of nitrendipine has been studied in seven elderly patients with chronic renal failure (CRF) and in six control subjects (mean creatinine clearance 30 and 97 ml·min−1 respectively). Racemic nitrendipine 20 mg was given once daily for seven days and the pharmacokinetics of the enantiomers over the last dosage interval were determined using a stereospecific assay. In both groups nitrendipine exhibited stereoselective pharmacokinetics (AUC, Cmax), but the half-lives of the enantiomers did not differ in individual subjects. As an index of stereoselectivity, the mean S/R ratio of AUCs in control subjects (2.07) was not significantly different from the ratio in patients with CRF (2.68). The mean AUCs of (S)- and (R)-nitrendipine during the last dosage interval were increased in CRF by 132% and 85%, respectively. The observed doubling of the half-lives and the increases in Cmax did not reach significance because of the large variability in each group. Thus, the pharmacokinetics of oral nitrendipine is altered in CRF, but there was no change in the stereoselectivity of its pharmacokinetics.
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