EFFECTS OF VARIOUS FACTORS ON STEADY-STATE PLASMA-CONCENTRATIONS OF TRAZODONE AND ITS ACTIVE METABOLITE M-CHLOROPHENYLPIPERAZINE

Effects of various factors on steady state plasma concentrations of tr azodone and its active metabolite m-chlorophenylpiperazine (mCPP) were studied in 43 depressed patients (19 males, 24 females) receiving tra zodone 150 mg at bedtime for 1-3 weeks, Sixteen cases were smokers, an d 19 cases were also receiving various benzodiazepines. The means (and ranges) of plasma concentrations of trazodone and mCPP, and the mCPP/ trazodone ratio were 619 (251-1059) ng/ml, 59 (32-139) ng/ml and 0.100 (0.044-0.219), respectively. Smokers had significantly (p < 0.05) low er plasma concentrations of trazodone and higher mCPP/trazodone ratios than non-smokers, Age, sex and co-administration of benzodiazepines d id not affect any plasma concentrations or the mCPP/trazodone ratio, I n 11 cases where the dose was increased to 300 mg, neither plasma conc entration/dose ratios nor the mCPP/trazodone ratio changed significant ly, The present study thus suggests that: (1) there is a large interin dividual variation in the metabolism of trazodone; (2) smoking enhance s the metabolism, but age, sex and co-administration of benzodiazepine s do not affect it; (3) trazodone and mCPP have linear kinetics.