RELATIONSHIP BETWEEN THE CYP2D6 GENOTYPE AND THE STEADY-STATE PLASMA-CONCENTRATIONS OF TRAZODONE AND ITS ACTIVE METABOLITE M-CHLOROPHENYLPIPERAZINE

The relationship between the cytochrome P450 (CYP) 2D6 genotype and th e steady-state plasma concentrations (Css) of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) was studied in 54 depresse d Japanese patients receiving trazodone 150 mg at bedtime. By use of a llele-specific PCR analysis, the wild type allele, three mutated allel es causing absent enzyme activity (CYP2D6A, CYP2D6B and CYP2D6D) and o ne mutated allele causing decreased enzyme activity (CYPZD6 Ch) were i dentified. The means (ranges) of the Css of trazodone, corrected to th e median body weight in 17 cases with no mutated allele, 27 cases with one mutated allele and 10 cases with two mutated alleles, were 556 (2 81-1115), 643 (302-1362) and 671 (234-1418) ng/ml, respectively, while the values of mCPP were 60 (35-121), 65 (33-99) and 58 (38-112) ng/ml , respectively. Neither the Css of trazodone (F = 0.80, P = 0.45) nor that of mCPP (F = 0.49, P = 0.61) significantly differed among the thr ee groups. The present study thus suggests that the CYP2D6 genotype ca nnot predict the Css of these compounds.