The plasma kinetics of a nifedipine/acebutolol fixed dose combination were estimated after a single oral dose in patients with chronic liver disease and in a healthy control group of the same age. The drug metabolism evidently slowed down in the group with chronic liver disease. The plasma elimination half-lives of acebutolol, diacetolol and nifedipine of these patients were about twice as long as that in the control group. Doses of these drugs should be accordingly reduced, particularly in cirrhosis.

Acebutolol↗

PubMed1988

Lack of interaction between zolpidem and H2 antagonists, cimetidine and ranitidine.

Zolpidem is a new imidazopyridine derivative acting as a hypnotic which may be prescribed with H2 receptor antagonists in patients with peptic ulcer. A cross-over study (cimetidine, 1 g daily for 19 days; ranitidine, 300 mg daily for 19 days; wash-out period: 20 days) was carried out in six healthy volunteers. Zolpidem, 20 mg was administered orally at 09h00 prior to any treatment and on days 2 and 17 of each treatment period. Antipyrine clearance was also determined before and on day 18 of each treatment period. Under these experimental conditions, the inhibitory effect of cimetidine on the Cyt P-450 mono-oxygenase system has been demonstrated (reduced clearance of antipyrine, p less than 0.01) but the pharmacokinetics of zolpidem did not appear to be modified. Zolpidem induced hypnotic effects for the first 3 h which tend to be prolonged by the combination with cimetidine. Psychometric and pharmacokinetic evaluations did not show significant interactions with either anti-H2 receptor agent following zolpidem administration.

Adult↗

PubMed1988

Changes in plasma activities of lipolytic enzymes and lipids of normolipidemic subjects given phenobarbital, a strong microsomal inducer, alone or in combination with fenofibrate.

Eight male, normolipidemic, non-obese subjects were given fenofibrate (F) (300 mg daily) for eight days (period F). After a wash-out period of four weeks, phenobarbital (P) (100 mg daily) was given for eight days (period P). At the end of this period, P was continued at the same dosage but F (300 mg daily) was added and both drugs were given simultaneously for a further eight-day period (period P + F). The plasma concentrations of lipids and the plasma activities of enzymes involved in the interconversion of plasma lipoproteins: lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyltransferase (LCAT) were measured before and at the end of each period of treatment. Fenofibrate induced a decrease in the plasma concentration of triglycerides (TG), total cholesterol (TC), apoB and an increase in the plasma activities of LPL and LCAT. Phenobarbital induced a decrease in the plasma concentration of TC, HDL-C and LDL-C (with an unchanged HDL-C/LDL-C ratio) and in the plasma activity of LPL. Addition of P to F did not modify the hypolipidemic action of F but the increase of LPL activity during period P + F was found to be greater than that observed during period F. It is concluded that P does not modify the serum lipoprotein pattern in a way which can be considered as beneficial in terms of atherosclerosis. By measuring the serum concentration of unconjugated bilirubin, the plasma clearance of antipyrine and the urinary excretion of 6 beta-hydroxycortisol as parameters of hepatic microsomal induction, F appeared to be a slight inducer as compared with P. Thus, enzyme induction cannot explain the changes in serum lipoproteins induced by P and does not modify the hypolipidemic action of F.

Adult↗

PubMed1987

Short-term effects of beta blockers atenolol, nadolol, pindolol, and propranolol on lipoprotein metabolism in normolipemic subjects.

The short-term effect of the blockade of the beta-adrenergic receptors on serum lipoproteins and the plasma activities of the enzymes involved in the metabolism of the serum lipoproteins: lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyltransferase (LCAT) was evaluated in ten healthy normolipemic and normotensive subjects. In the first part of the study, the first three-day period of placebo was followed by another three-day period during which propranolol (120 mg/d) was given. In the second, third, and fourth part of the study, the same schedule was used but pindolol (15 mg/d), nadolol (160 mg/d), atenolol (100 mg/d) were given respectively instead of propranolol. The four drugs induced a significant blockade of the beta-adrenergic receptors as evaluated by the measurement of the double two-step test of Master (-45%). Despite similar blockade, the effect on serum lipid concentrations depended on the type of drug: propranolol induced an increase in triglycerides and apoprotein B-concentrations and a decrease in serum high density lipoprotein cholesterol (HDL-C) and apoprotein AI-concentrations. Pindolol provoked only a slight decrease of serum HDL-C concentration. Nadolol and atenolol elicited a lowering of the same magnitude in HDL-C. Except for a possible slight increase in plasma LCAT activity on propranolol, there was no significant change in the plasma activities of LPL, HL, and LCAT during the blockade of the beta-adrenergic receptors with the drugs used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1987