Rifampin, a cytochrome P450 3A inducer, decreases plasma concentrations of antipsychotic risperidone in healthy volunteers

Background Although cytochrome P450 (CYP) 2D6 is often thought to be the only CYP responsible for the metabolism of risperidone, many reports suggest that CYP3A may be involved too. Rifampin, a potent CYP3A inducer, has been known to markedly decrease plasma concentrations of various drugs, which are concomitantly administered during treatment. Objective To examine the effect of rifampin on plasma concentrations of a single oral dose of risperidone in healthy Thai male volunteers. Methods In an open, randomized two-phase crossover study, separated by a 2-week period, 10 healthy Thai male volunteers received a single oral dose of 4-mg risperidone alone or with 600 mg rifampin, orally once daily for 5 days. Serial blood samples were collected at specific time points for a 48-h period. Risperidone was measured in plasma using high performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined by using non-compartmental analysis. Results Co-administration with 600-mg rifampin once daily for 5 days was associated with a significant decrease in risperidone area under the curve (AUC(0-48)) and maximal concentration (C-max) by 72% (157.49 +/- 48.80 vs. 42.66 +/- 7.81 ng/L/h; P < 0.01) and 50% (32.44 +/- 6.05 vs. 16.16 +/- 2.73 ng/mL; P < 0.05), respectively when compared with risperidone alone. Conclusions Rifampin when used concurrently with risperidone significantly decreases the plasma concentration of risperidone. Our results provide in vivo evidence of the involvement of CYP3A in the metabolism of risperidone, in addition to CYP2D6. Thus, co-administration of risperidone with CYP3A inducer(s), including rifampin should be recognized or avoided in clinical practice.