title: Free and glucuronidated olanzapine serum concentrations in psychiatric patients: influence of carbamazepine comedication.
abstract: The influence of carbamazepine on the glucuronidation of the antipsychotic olanzapine was studied in a group of psychiatric patients. Steady-state serum concentrations of free and glucuronidated olanzapine were measured in 31 psychiatric patients in monotherapy (dose range, 2.5-30 mg/d; median, 15 mg/d) and in 16 patients being comedicated with carbamazepine (dose range, 5-50 mg/d; median, 20 mg/d). The concentrations were determined by HPLC with and without acid hydrolysis of glucuronidated olanzapine. For the monotherapy group, the concentrations of free and glucuronidated olanzapine ranged from 0 nmol/L to 292 nmol/L (median, 94 nmol/L) and from 0 nmol/L to 180 nmol/L (median, 27 nmol/L), respectively. The serum concentrations of the carbamazepine-treated group ranged from 21 nmol/L to 310 nmol/L (median, 81 nmol/L) and from 0 to 376 nmol/L (median, 57 nmol/L) for free and glucuronidated olanzapine, respectively. Two patients with outlying values were excluded from further analysis. The median concentration-to-daily dose ratios (C/D) of free and glucuronidated olanzapine in the monotherapy group were 5.8 nmol/L/mg and 2.2 nmol/L/mg, respectively (n =30). The corresponding values for the group comedicated with carbamazepine were 3.6 and 3.1 nmol/L/mg (n =15). Thus, the median C/D of free olanzapine in the carbamazepine group was 38% lower than that of the monotherapy group (P <0.01), confirming that carbamazepine accelerates the metabolism of olanzapine. Further, for the carbamazepine group the median glucuronidated olanzapine fraction constituted 79% of the free fraction compared with 43% for the monotherapy group (P <0.01), which suggests that an increased rate of olanzapine glucuronidation contributes to the increased rate of metabolism of olanzapine induced by carbamazepine.
authors.affiliation: Department of Biological Psychiatry, Psychiatric University Hospital, Risskov, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Linnet
authors.forename: Ole V
authors.initials: OV
authors.lastname: Olesen
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000097:blood* / Q000493:pharmacokinetics; D001569:Benzodiazepines; D002220:Carbamazepine / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D020719:Glucuronides / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D011618:Psychotic Disorders / Q000097:blood*
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D020719:Glucuronides; D001569:Benzodiazepines; D002220:Carbamazepine; D010890:Pirenzepine; D000077152:Olanzapine