In vitro metabolism of citalopram by monoamine oxidase B in human blood

The metabolism of the antidepressant citalopram (CIT) by monoamine oxidase B (MAO-B) was studied in vitro. In incubations with blood of nine healthy volunteers R-(P=0.015) and S-(P=0.0034) CIT propionic acid (CITPROP) production was correlated with the number of platelets. S-CITPROP production was 5.6 times higher than R-CITPROP production and in incubations containing the MAO-B inhibitor deprenyl, racemic CITPROP production was diminished to 9.1%. To our knowledge, this is the first time that MAO-B activity in blood is shown with an antidepressant as substrate. As MAO is strongly expressed in human brain, this observation suggests that this enzymatic system may be implicated in drug metabolism in the CN

Increased (R)-methadone plasma concentrations by quetiapine in cytochrome P450s and ABCB1 genotyped patients

Steady-state plasma concentrations of (R)- (ie, the active form), (S)-, and (R,S)-methadone were measured in 14 addict patients in methadone maintenance treatment, before and after introduction of quetiapine, administered at a mean dosage of 138 mg/d (SD, 87 mg/d; median, 125 mg/d; range, 50-300 mg/d) during a mean period of 30 days (SD, 8 days; median, 30 days; range, 20-48 days). Eleven patients were genotyped as being CYP2D6 extensive metabolizers (EMs) and 3 patients as poor metabolizers. Eleven patients had the ABCB1 3435 CT or CC genotypes, and 3 patients had the ABCB1 3435 TT genotype, the latter genotype being associated with lower P-glycoprotein activity. Quetiapine significantly increases (R)-methadone concentration-dose ratios in the whole group [increase for (R)-methadone: mean, +21%; SD, +28%; median, +13%; range, -23% to +85%; P = 0.026], but not for (S)-methadone (mean, +23%; SD, +43%; median, +6%; range, -30% to +115%; P = 0.12) or for (R,S)-methadone (mean, +21%; SD, +34%; median, +9%; range, -21% to +95%; P = 0.064). The mean increases of (R)-methadone concentration-dose ratios were of 7%, 21%, and 30% in the CYP2D6 poor metabolizers, heterozygous EMs, and homozygous EMs, respectively, whereas they were of 3%, 23%, and 33% in the subjects with the ABCB1 3435 TT, CT, and CC genotypes, respectively. Thus, quetiapine increases the plasma concentrations of (R)-methadone, possibly in part by an interaction with CYP2D6 and/or with the P-glycoprotein transporter system. No signs of overmedication caused by increased methadone plasma concentrations were noticed by the staff or reported by the patients. (PsycINFO Database Record (c) 2007 APA, all rights reserved) (journal abstract