title: No influence of CYP3A43 rs472660G> A on steady-state serum olanzapine concentrations in white psychiatric patients.
abstract: The potential involvement of CYP3A43 in systemic olanzapine (OLA) metabolism has been suggested by one reported association between the intronic polymorphism CYP3A43 rs472660G>A and OLA clearance in 235 White and African-American patients. Trough plasma OLA concentrations in AA carriers were predicted on average 48% lower than in GG carriers. In the current study, we evaluated this finding by genotyping 374 White psychiatric patients on long-term OLA treatment. No significant difference in dose-adjusted trough serum OLA concentrations was observed between the seven AA carriers identified and the other two genotypes, without (P=0.6) or with (P=0.23) adjustment for additional covariates previously known to influence systemic OLA exposure. Because of the low prevalence of the rs472660 AA genotype in White populations (2%), larger study cohorts are needed for future association confirmation. Overall, CYP3A43 rs472660 is not likely to be a major contributor towards variability in systemic OLA exposure among White patients.
authors.affiliation: aDepartment of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden bCenter for Psychopharmacology, Diakonhjemmet Hospital cDepartment of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: Mao M
authors.initials: MM
authors.lastname: Söderberg
authors.forename: Espen
authors.initials: E
authors.lastname: Molden
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Dahl
mesh_terms: D001741:Black or African American / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D000077152:Olanzapine; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D001569:Benzodiazepines; D001189:Aryl Hydrocarbon Hydroxylases; C422408:CYP3A43 protein, human; D000077152:Olanzapine