Significant pharmacokinetic interaction between risperidone and carbamazepine: its relationship with CYP2D6 genotypes.

The effects of carbamazepine coadministration (400 mg/day for 1 week) on plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone were studied in 11 schizophrenic inpatients treated with 6 mg/day risperidone. Blood samplings were performed before and during carbamazepine coadministration, and 1 week after its discontinuation. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured using liquid chromatography-mass spectrometry-mass spectrometry. CYP2D6 genotypes were determined using the polymerase chain reaction method. Plasma concentrations of risperidone and 9-hydroxyrisperidone during carbamazepine coadministration (2.5+/-3.6 ng/ml and 19.4+/-4.1 ng/ml) were significantly ( P<0.01) lower than those before carbamazepine coadministration (5.0+/-7.9 ng/ml and 34.6+/-9.8 ng/ml). The changes in risperidone concentrations were positively correlated to the concentration ratios of risperidone/9-hydroxyrisperidone (r(s)=0.90, P<0.01), which were closely associated with CYP2D6 genotypes. The present study suggests that carbamazepine induces the metabolism of risperidone and 9-hydroxyrisperidone, and that the decrease in risperidone concentration is dependent on the CYP2D6 activity.