PT  - JOURNAL ARTICLE
AU  - Rikard Sandström
AU  - Hans Lennernäs
TI  - Repeated Oral Rifampicin Decreases the Jejunal Permeability of  <em>R/</em>S-Verapamil in Rats
DP  - 1999 Aug 01
TA  - Drug Metabolism and Disposition
PG  - 951--955
VI  - 27
IP  - 8
4099  - http://dmd.aspetjournals.org/content/27/8/951.short
4100  - http://dmd.aspetjournals.org/content/27/8/951.full
SO  - Drug Metab Dispos1999 Aug 01; 27
AB  - The main purpose of this rat study was to investigate the effect of rifampicin on the effective permeability (Peff) of R/S-verapamil in the rat jejunum. In addition the effect on metabolism of R/S-verapamil toR/S-norverapamil was examined. In situ single-pass perfusions of the rat jejunum were performed in animals pretreated with oral rifampicin (250 mg/kg/day) or saline (control) over various time periods (1, 4, 7, and 14 days). The jejunal Peff of each of the enantiomers of verapamil and d-glucose was estimated. The appearance ratios of the CYP3A-formed metabolites R- and S-norverapamil were also estimated in the outlet jejunal perfusate. The jejunal Peff of bothR- and S-verapamil decreased as an effect of the oral pretreatment with rifampicin. The appearance ofR- and S-norverapamil in the jejunum was also affected by the oral pretreatment with rifampicin, with increasing concentrations of R/S-norverapamil being evident after 14 days of rifampicin pretreatment. There was no stereoselectivity in either the Peff of R- andS-verapamil or the metabolic appearance ofR- and S-norverapamil. Treatment with oral rifampicin decreased the Peff ofR/S-verapamil, which is in accordance with an induction of P-glycoprotein activity in the apical enterocyte membrane. The increase in appearance of R/S-norverapamil in jejunum is in accordance with an induction of CYP3A metabolism in the rat. The American Society for Pharmacology and Experimental Therapeutics