Pharmacokinetic studies of propiverine hydrochloride (2). Metabolism in rats after single oral administration of P-4.

Abstract

Biotransformation of propiverine hydrochloride [1-methyl-4-piperidyl diphenylpropoxyacetate hydrochloride, P-4] was studied in rats after oral administration of P-4.1. The presence of nine metabolites of P-4 was found in the urine and the bile after oral administration ; they were identified based on a 1H-NMR and Mass spectra by direct comparison with authentic compounds.2. Portal plasma concentration of unchanged drug after oral administrati on of 14C-P-4 was 4 ?? 16 times higher than in peripheral plasma, indicating the presence of the hepatic first pass effect.3. After oral administration of 14C-P-4, 1-methyl-4-piperidyl benzilate N-oxide [DPr-P-4 (N → O)] was mainly excreted to the urine, unidentified polar metabolites, benzilic acid [BA], diphenyl-1-(2-hydroxy) propoxyacetic acid [ω-1-OH-Pr-BA], 2, 2-diphenyl-5-methyl-1, 4-dioxan-3-one [ω1-OH-Pr-BA(L)], 1-methyl-4-piperidyl diphenyl-(2-carboxy) ethoxyacetate [ω-COOH-P-4] were excreted to the bile.4. Conjugates (glucuronide and sulfate) accounting for only 3 ?? 4 % of administered dose were detected in the urine and bile.