1. Effects of various factors including the CYP2D6 genotype and coadministration of flunitrazepam on the steady-state plasma concentrations of bromperidol and its reduced metabolite.
- Author
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Suzuki, A., Otani, K., Mihara, K., Yasui, N., Kondo, T., Tokinaga, N., Furukori, H., Kaneko, S., Inoue, Y., and Hayashi, K.
- Subjects
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CYTOCHROME P-450 , *FLUNITRAZEPAM , *POLYMERASE chain reaction , *PHYSIOLOGY - Abstract
Abstract The effects of various factors, including the cytochrome P450 (CYP) 2D6 genotype and the coadministration of flunitrazepam, on the steady-state plasma concentrations (Css) of bromperidol and its reduced metabolite were studied in 62 schizophrenic inpatients receiving bromperidol 12 mg/day. By use of allele-specific PCR analysis, the wild type allele (CYP2D6*IA) and four mutated alleles causing either absent (CYP2D6*3, CYP2D6*4 and CYP2D6*5) or decreased (CYP2D6*10) CYP2D6 activity were identified. The means (ranges) of the Css of bromperidol and reduced bromperidol corrected to the median body weight were 7.2 (1.3-17.4) and 2.2 (0.4-8.9) mg/ml, respectively. Neither the Css of bromperidol nor that of reduced bromperidol significantly differed among the patients with no (n = 28), one (n = 30) and two mutated alleles (n = 4). The patients coadministered with flunitrazepam (n = 52) had significantly (P < 0.05) higher Css of bromperidol, but not reduced bromperidol, than those not (n = 10). Age, sex and smoking had no significant effects on the Css of these compounds. The present study thus suggests that the polymorphic CYP2D6 is not involved in the metabolism of... [ABSTRACT FROM AUTHOR]
- Published
- 1998
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