The metabolism of 2,3-trans-3,4-trans-3,5,7,3',4'-pentahydroxy-4-(2,4,6-trihydrox yphenyl)-flavan and 2,3-trans-3,4-trans-3,5,7,3',4',-pentahydroxy-4-(2,3-trans-3,5,7,3 ', 4'-pentahydroxyflavanyl-[8])-flavan in vitro by rat-caecal microflora was investigated. Metabolites were extracted and enriched by column chromatography and preparative h.p.l.c., while structural determination was carried out using comparative g.l.c.-mass spectrometry and p.m.r. spectrometry. The metabolites identified were derivatives of benzoic acid, phenylacetic acid, phenylpropionic acid and phenyllactic acid in addition to phloroglucinol, delta-(3-hydroxyphenyl)-gamma-valerolactone and 1-(3-hydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)-propan-2-ol. An additional metabolic route, which differs from the expected severance of the (+)-catechin-phloroglucinol bond and well-documented total heterocyclic ring degradation of flavanoids, is proposed.

The metabolism of (+)-catechin by rat-caecal microflora in vitro was investigated. Metabolites were isolated by column chromatography, preparative t.l.c. and h.p.l.c., while structural allocation was aided by mass spectrometry and proton magnetic resonance. In contrast with the well-documented total heterocyclic ring cleavage of flavanoids, (+)-catechin was found to undergo partial heterocyclic ring cleavage of two novel diarylpropan-2-ol metabolites. p-Dehydroxylation of (+)-catechin predominates during its degradation to the diarylpropanol metabolites.

Twenty-six healthy males took part in this double-blind, randomised, placebocontrolled, two-period, cross-over study. Pantoprazole (40 mg) (test) or placebo (reference) were administered once daily, for 8 days, with a 3 week washout period. A single oral dose of 25 mg warfarin sodium was co-administered with pantoprazole or placebo on Day 2 of each treatment period. The 90% confidence intervals for the 'test/reference' mean ratios of the excess AUC(0,168h) of prothrombin time and AUC(0,168 h) of factor VII, and of Cmax, AUC and t112 of both R-and S-warfarin fell within the equivalence range of 80% to 125%. These results suggest that pantoprazole does not alter the pharmacokinetics or pharmacodynamics of warfarin.

Aims Triptorelin is a gonadotropin-releasing hormone (GnRH) analogue with enhanced affinity for GnRH receptors and a prolonged half-life due to its resistance to enzymatic degradation. The sustained-release formulation of this molecule is advantageous in conditions requiring chronic hormone suppression. Methods This was an open study to determine the pharmacokinetics of a single i.v. bolus dose of 0.5 mg triptorelin acetate in four groups of six male subjects; namely in healthy subjects (Group I), in patients with varying degrees of renal insufficiency (Groups II and III), and in patients with hepatic insufficiency (Group IV). Results The maximum concentrations of triptorelin were found to be similar for all four study groups (geometric mean C max between 41.6 mg ml −1 and 53.9 mg ml −1). The total clearance of triptorelin decreased with increasing renal impairment, and was even lower in patients with hepatic insufficiency (geometric mean CL tot : 210 ml min −1 , 113 ml min −1 , 86.8 ml min −1 and 57.3 ml min −1 for Groups I, II, III and IV, respectively). Serum triptorelin concentrations in all four groups were adequately described by a three-compartment model. The elimination half-life for patients with hepatic impairment was similar to that of patients with renal impairment (geometric mean t 1/2, z : 6.6 h, 7.7 h and 7.6 h for Groups II, III and IV, respectively), but significantly longer than in healthy volunteers (2.8 h for Group I). The first and second distribution half-lives were similar for the four groups studied, with geometric mean distribution half-lives of about 0.1 h (6 min) and 0.75 h (45 min), respectively. Conclusions Although both renal and hepatic function are important for the clearance of triptorelin, the liver plays the predominant role in subjects suffering from some degree of renal impairment.

Twenty-four (24) Caucasian male subjects completed a single-blind, randomised, three-treatment, three-period, cross-over study. In each treatment phase, subjects received a single dose of 144 mg pipamperone dihydrochloride (CAS 2448-68-2) (equivalent to 120 mg pipamperone; CAS 1893-33-0) as either the reference product (3 x 40 mg tablets), test product A (3 x 40 mg tablets) or test product B (1 x 120 mg tablet). Each consecutive dosing was separated by a washout period of 14 days. Following each dosing, venous blood samples were collected over a period of 120 h for the determination of plasma pipamperone concentrations by high-performance liquid chromatography. The most common drug related adverse events, ranging from mild to moderate in intensity, were bloodshot eyes, nasal congestion, dry mouth, hypotension and dizziness. The geometric mean Cmax of pipamperone for both the reference product and test product A was 266 ng/ml and for test product B 263 ng/ml. The geometric mean AUC0-infinity was 3107 ng.h/ml for the reference product, 3229 ng.h/ml for test product A and 3108 ng.h/ml for test product B. The two test products were shown to be bioequivalent to the reference product with respect to all pharmacokinetic variables investigated.