Toward pharmacogenetic SLCO1B1-guided dosing of methotrexate in arthritis using a murine Slco1b2 knockout model.

ABSTRACT: Low-dose methotrexate (MTX) is a first-line therapy for the treatment of arthritis. However, there is considerable interindividual variability in MTX exposure following standard dosing. Polymorphisms in SLCO1B1 significantly effect MTX clearance, altering therapeutic response. One decreased function variant, rs4149056 (c.521T>C, Val174Ala), slows MTX clearance and in vitro uptake of MTX. This phenotype was recapitulated in a mouse model using a knockout (KO) of the murine orthologue, Slco1b2. Our objective was to investigate the impact of this phenotype on the pharmacokinetics and therapeutic outcomes of low-dose MTX in a murine model of collagen-induced arthritis (CIA). We evaluated response to MTX in mice with CIA using wildtype (WT), heterozygous, and KO Slco1b2 mice on a DBA1/J backgro

SUBMITTER: Taylor ZL 

PROVIDER: S-EPMC8604247 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature