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.
Ono
Shingo
S
Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan. rak@cc.hirosaki-u.ac.jp
Mihara
Kazuo
K
Suzuki
Akihito
A
Kondo
Tsuyoshi
T
Yasui-Furukori
Norio
N
Furukori
Hanako
H
de Vries
Ronald
R
Kaneko
Sunao
S
D000328:Adult; D002220:Carbamazepine / Q000097:blood*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004347:Drug Interactions / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018967:Risperidone / Q000097:blood*; D012559:Schizophrenia / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D018709:Statistics, Nonparametric
D002220:Carbamazepine; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone