Oral bioavailability of phenobarbital: a comparison of a solution in Myvacet 9-08, a suspension, and a tablet.

Purpose: A three-way crossover study with seven healthy male volunteers was conducted to determine the relative bioavailability of phenobarbital after single dose administration of 100 mg of phenobarbital as oral solution in Myvacet 9-08, and as a suspension, compared with a 100 mg phenobarbital tablet.

Materials And Methods: At 4-week intervals each subject received the solution in Myvacet 9-08, the suspension and the tablet in randomized order. Blood samples were collected for 48 h after each dose for analysis of phenobarbital.

Comparative single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following a new dual-release and a conventional slow-release formulation of levodopa and benserazide in healthy subjects.

A multiple-dose study was performed to assess the pharmacokinetic profile of a new levodopa/benserazide dual-release formulation (DRF) in comparison with a conventional slow-release formulation (SRF). The study was of an open label, randomized, two-way cross-over design and was conducted in 18 subjects. Assessment of the two formulations was at day 1 (single-dose) and at day 7 after a 5-day t.

Pharmacokinetics of imidapril and its active metabolite imidaprilat following single dose and during steady state in patients with chronic renal failure.

Objective: An open study on the single dose and steady-state pharmacokinetics of imidapril, a novel prodrug-type angiotensin-converting enzyme (ACE) inhibitor, and its active metabolite imidaprilat was conducted in eight patients with moderate chronic renal failure [mean creatinine clearance (CL(CR)) 64 ml x min(-1); range 42-77 ml x min(-1)], eight patients with severe chronic renal failure (mean CL(CR), 18 ml x min(-1); range 11-29 ml x min(-1)) and eight healthy volunteers with normal renal function. Subjects received an oral dose of 10 mg imidapril once per day for 7 days.

Results: No statistical differences of either maximum concentration (Cmax) or the area under the curve (AUC) were found between patients with moderate renal failure and healthy subjects.

Pharmacokinetic studies with a dual-release formulation of levodopa, a novel principle in the treatment of Parkinson's disease.

The objectives of the two studies reported here were the investigation of the influence of tablet breaking and food on the pharmacokinetics of levodopa and 3-O-methyldopa (3-OMD) after administration of a new levodopa/benserazide formulation with a biphasic drug delivery profile (Madopar DR). Both studies had an open-label, randomised, two-way crossover design and were conducted in 12 healthy young subjects. The pharmacokinetics of levodopa and 3-OMD after one intact or two halved tablets were very similar with average Cmax and tmax 1.

Pharmacokinetics of imidapril and its active metabolite imidaprilat following single dose and during steady state in patients with impaired liver function.

Objective: The possible influence of impaired liver function on the pharmacokinetic disposition of imidapril, a novel prodrug type angiotensin-converting enzyme (ACE) inhibitor, and its active metabolite, imidaprilat, was investigated.

Methods: Eight subjects with normal liver function and eight patients with liver dysfunction received an oral dose of 10 mg imidapril once daily for 7 days.

Results: Plasma imidapril concentrations after single and, although less pronounced, after repeated dosing were higher in the liver disease patients, whereas imidaprilat concentrations were lower.

Bioequivalence and relative bioavailability of a new diltiazem sustained release formulation.

The bioequivalence and relative bioavailability of a new sustained release formulation of diltiazem (120 mg, Diltiazem-Mepha 120 retard, CAS 33286-22-5) in comparison with a 120 mg reference formulation was investigated in a randomised 2-way cross-over study in 18 healthy volunteers following multiple, twice daily dosing for 5 days. Blood samples were taken prior to the morning dose on days 1 to 4 and before and periodically during 32 h after the last administration in the morning of day 5. The diltiazem concentration was determined using a HPLC method.

Relationship between glutathione content in liver and glutathione conjugation rate in the rat in vivo. Effect of buthionine sulphoximine pretreatment on conjugation of the two 2-bromoisovalerylurea enantiomers during intravenous infusion.

The relationship between hepatic glutathione content and hepatic glutathione conjugation rate in the rat in vivo was investigated. As substrate for glutathione conjugation, racemic (R,S)-2-bromoisovalerylurea (BIU) was used which gives rise to the biliary excretion of two diastereoisomeric glutathione conjugates and the urinary excretion of two diastereoisomeric mercapturates. The excretion rate of the glutathione conjugate in bile reflects hepatic conjugation exclusively.