ArticleClinical and translational science2026
Pharmacogenetic hSLCO1B1*14-Guided Dosing of Methotrexate in Transgenic Arthritic Mice Normalizes Exposure and Response.
Article in Clinical and translational science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Pharmacogenetic hSLCO1B1*14-Guided Dosing of Methotrexate in Transgenic Arthritic Mice Normalizes Exposure and Response.Clinical and translational science · 2026Article
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11 authors.
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Abstract
Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease that negatively affects ~100,000 children under the age of 16 in the United States. About ~30% of these patients fail first-line drug therapy with low-dose methotrexate (MTX) due to poor tolerability or lack of efficacy. The SLCO1B1*14 allele is associated with increased MTX clearance and has been linked to reduced overall drug exposure and nonresponse to MTX in JIA patients. Herein, we describe transgenic hSLCO1B1*14 and hSLCO1B1*1 DBA1/J mSlco1b2 knock-out mice, which we used to assess arthritic response to MTX using the collagen-induced arthritis model. Mass spectrometry-based proteomics analysis revealed that OATP1B1 protein abundance was 2.1-fold higher in hSLCO1B1*14 mice compared to hSLCO1B1*1 mice. Following treatment with 1 mg/kg MTX for 3 weeks, hSLCO1B1*14 mice exhibited a 39% increase in median arthritic disease burden (p = 0.02) and a 22% reduction in MTX AUC (p = 0.14) compared to hSLCO1B1*1 mice. Pharmacokinetic modeling estimated that the hSLCO1B1*14 mice would need a 30% higher dose to equalize exposure and response to hSLCO1B1*1 mice. When hSLCO1B1*14 mice received 1.3 mg/kg MTX, the arthritic disease burden and overall MTX exposure were less than the 1 mg/kg MTX in hSLCO1B1*1 mice, reinforcing that differences in MTX elimination and therapeutic response can be accounted for by using pharmacogenetic-guided dosing of MTX in JIA patients.
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