Impact of the transcription factor nuclear factor 1 B T>C polymorphism on clozapine metabolism in vivo and expression of intestinal transporters in vitro.

ABSTRACT: Clozapine's (CLZ) pharmacokinetics involves multiple enzymes and transporters, which may be influenced by genetic variability. A variant in the nuclear factor I B (NFIB) gene (rs28379954 T>C) has been associated with reduced CLZ serum concentrations. This study explored CLZ metabolism in relation to NFIB genotype in patients with known smoking habits. NFIB's role in regulating gene expression of transporters relevant for intestinal absorption of CLZ was investigated using Caco-2/TC7 cells. Metabolite spectra of CLZ-treated patients (n = 285) were included from a therapeutic drug monitoring service. Formation of 30 CLZ metabolites was compared between patients carrying NFIB CT and TT diplotypes. To investigate NFIB's possible role in regulating the expression of drug transporters of relevan

SUBMITTER: Solbakk M 

PROVIDER: S-EPMC12405907 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature