|Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Nowadays, main therapeutic tools for mental disorders are pharmacotherapies. However, most of the psychiatrists prescribe the psychotropic drugs with no guideline or no theoretical background. In order to obtain "maximum clinical effect with minimum side effect" of the psychotropic drugs, we need to collect and utilize the information of the individual patients including the pharmacogenomic information and comprehensively analyze such information. In this research project, we tried to find the relationship between the activity of drug metabolizing enzyme such as cytochrome P450 or glucuronyl transferase (genotypes of drug metabolizing enzymes), genotypes of serotonin-noradrenaline transporter and the clinical effect of selective serotonin reuptake inhibitor and serotonin-noradrenaline reuptake inhibitor. In 2001, samples from 12 patients with affective disorders treated with paroxetine were analyzed. They were maintained at the same daily dose at least for two weeks to obtain steady state concentrations. Significant positive correlation between plasma concentrations of paroxetine and daily dose corrected for body weight was observed, however, no significant relationship between the genotype of cytochrome P450 and the plasma levels of paroxetine was found. In 2002, the samples from 44 patients treated with paroxetine were analyzed. The patients with 20, 30, 40mg/day of paroxetine showed 3.0, 6.66, 6.24 fold plasma concentrations compared to the drug concentrations in the patients with 10mg/day, respectively, which means non-linear pharmacokinetics of paroxetine. Again, no significant relationship between the genotype of cytochrome P450 2D6 and the plasma levels of paroxetine was found.