Pharmacokinetics and metabolism of indoprofen in the hamster

Abstract

2-[p-(1-Oxo-2-isoindolinyl)phenyl]propionic acid (indoprofen) is rapidly absorbed after oral administration (2 mg/kg) to male and female hamsters. Peak plasma levels of about 12-13 microgram/ml are reached within 1 h of dosing. Plasma concentrations in males and females are similar until 4 h but different at subsequent observation times. The half-life of indoprofen in plasma is approximately 7 h for males and 16 h for females. In experiments with 14C-labelled compound, radioactivity is mainly excreted in the urine: 94% of the dose in 6 days for males and 73% in 5 days for females. The females also excrete a significant amount of the drug (22%) in the faeces, probably via the bile. Residual radioactivity in female carcasses on the 5th day represents 1% of the dose. The main excretory product is the unchanged drug as such (about 35% and 21%, respectively, in 0-24 hour urine for males and females) and as glucuronic acid conjugate (29% and 12%). Small amounts of 5- and 6-hydroxy-isoindolinyl derivatives, and of two metabolites whose structures have not been identified, are also found in the urine of the animals of both sexes.