Effect of Organic Anion Transporting Polypeptide 1B1 on Plasma Concentration Dynamics of Clozapine in Patients with Treatment-Resistant Schizophrenia.

ABSTRACT: The involvement of drug-metabolizing enzymes and transporters in plasma clozapine (CLZ) dynamics has not been well examined in Japanese patients with treatment-resistant schizophrenia (TRS). Therefore, this clinical study investigated the relationship between single nucleotide polymorphisms (SNPs) of various pharmacokinetic factors (drug-metabolizing enzymes and transporters) and dynamic changes in CLZ. Additionally, we aimed to determine whether CLZ acts as a substrate for pharmacokinetic factors using in vitro assays and molecular docking calculations. We found that 6 out of 10 patients with TRS and with multiple organic anion transporting polypeptide (OATP) variants (OATP1B1: *1b, *15; OATP1B3: 334T>G, 699G>A; and OATP2B1: *3, 935G>A, 601G>A, 76_84del) seemed to be

SUBMITTER: Sato T 

PROVIDER: S-EPMC11642635 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature