title: Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine.
abstract: Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were studied in 43 depressed patients (19 males, 24 females) receiving trazodone 150 mg at bedtime for 1-3 weeks. Sixteen cases were smokers, and 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) lower plasma concentrations of trazodone and higher mCPP/trazodone ratios than non-smokers. Age, sex and co-administration of benzodiazepines did not affect any plasma concentrations or the mCPP/trazodone ratio. In 11 cases where the dose was increased to 300 mg, neither plasma concentration/dose ratios nor the mCPP/trazodone ratio changed significantly. The present study thus suggests that: (1) there is a large Interindividual variation in the metabolism of trazodone; (2) smoking enhances the metabolism, but age, sex and co-administration of benzodiazepines do not affect it; (3) trazodone and mCPP have linear kinetics.
authors.affiliation: Department of Neuropsychiatry, Hirosaki University Hospital, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ishida
authors.forename: K
authors.initials: K
authors.lastname: Otani
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Ohkubo
authors.forename: T
authors.initials: T
authors.lastname: Osanai
authors.forename: N
authors.initials: N
authors.lastname: Yasui
authors.forename: K
authors.initials: K
authors.lastname: Mihara
authors.forename: H
authors.initials: H
authors.lastname: Higuchi
authors.forename: K
authors.initials: K
authors.lastname: Sugawara
mesh_terms: D000328:Adult; D001569:Benzodiazepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010599:Pharmacokinetics; D010879:Piperazines / Q000097:blood* / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000097:blood* / Q000378:metabolism*; D012737:Sex Factors; D012907:Smoking; D014196:Trazodone / Q000097:blood* / Q000378:metabolism*
chemical_list: D010879:Piperazines; D017366:Serotonin Receptor Agonists; D001569:Benzodiazepines; C015068:1-(3-chlorophenyl)piperazine; D014196:Trazodone