[Effect of smoking on pharmacokinetics of antipsychotics]

The population of Japanese smokers has decreased; however, the prevalence of smokers among psychiatric patients has been reported to be as high as 80% in schizophrenic patients. Although the impact of smoking on the pharmacokinetics of antipsychotics has been reported, results have been controversial. At first, the impact of smoking on plasma haloperidol (HAL) concentrations was investigated in Japanese male schizophrenic inpatients treated with HAL per os. Smokers had approximately 20% lower HAL concentrations/daily dose of HAL/kg body weight than non-smokers. The impact of genetic polymorphism of CYP1A2 that are related to the induction of the isozyme on the plasma levels of HAL in male smokers with schizophrenia was also investigated. A point mutation from C to A in intron 1 at position 734 and a point mutation from G to A at position--2964 in the 5'-flanking region of CYP1A2 were identified by the PCR-RFLP method. Regarding C/A polymorphism in intron 1 at position 734, no significant difference was found in the plasma concentrations of HAL corrected for dose and weight among the subjects with A/A, A/C and C/C genotypes. Regarding G/A polymorphism at position--2964 in the 5'-flanking region, no significant difference was found in the plasma concentrations of HAL corrected for dose and weight between subjects with G/G and G/A.