Effects of Oral Rutaecarpine on the Pharmacokinetics of Intravenous Chlorzoxazone in Rats.

ABSTRACT

It has been reported that hepatic microsomal cytochrome P450 (CYP) 2E1 is responsible for the metabolism of chlorzoxazone (CZX) to 6-hydroxychlorzoxazone. The present study was undertaken to assess the possible interaction of rutaecarpine, an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa, with CZX. Male Spraque-Dawley rats were administered with 80 mg/kg/day of oral rutaecarpine for three consecutive days. Twenty four hr after the pre-treatment with rutaecarpine, the rats were treated with 20 mg/kg of intravenous CZX Rat hepatic microsomes isolated from rutaecarpine-treated rats showed greater (50% increase) activity of p-nitrophenol hydroxylase (a marker of CYP2E1) when compared with the control rats. Compared with control rats, the AUC of CZX was significantly smaller (84% decrease) possibly due to significantly faster CL (646% increase) in rats pretreated with rutaecarpine. This could be, at least partially, due to induction of CYP2E1 by rutaecarpine.