Calcitriol-mediated modulation of organic anion transporters: Insights from endo...

연구 요약

Calcitriol-mediated modulation of organic anion transporters: Insights from endogenous biomarkers and methotrexate pharmacokinetics.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 학술지에 발표된 이 연구는 Vo DK, Nguyen TT, Joo SA 외 연구팀이 수행하였습니다.

이 연구는 'Calcitriol-mediated modulation of organic anion transporters: Insights from endogenous biomarkers and methotrexate pharmacokinetics.'에 대한 과학적 분석을 제공합니다.

핵심 내용

This study aimed to investigate the effects of calcitriol on endogenous biomarkers taurine and pyridoxic acid (PDA) associated with the organic anion transporters Oat1 and Oat1/3, respectively, and compare these changes with those observed for the clinical substrate, methotrexate (MTX). Male rats were administered intraperitoneal (i.p.) injections of either vehicle (maize oil) or calcitriol (2.56 nmol/kg/day) for 4 consecutive days. Plasma, urine, and tissue samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Calcitriol markedly increased plasma taurine levels, decreased its urinary excretion, and reduced taurine concentrations in most tissues. In contrast, PDA exhibited only a moderate increase in plasma levels, with no significant change in urinary excretion, but a notable increase in kidney concentrations. Additional probenecid inhibition studies supported the Oat1-mediated modulation. Intravenous (i.v.) pharmacokinetic studies of taurine (10 mg/kg) revealed altered plasma exposure, clearance, and tissue distribution following calcitriol and probenecid inhibition. In addition, calcitriol significantly affected MTX pharmacokinetics, reinforcing its effect on Oat1/3 function. Taurine induced more significant changes than PDA, indicating its greater sensitivity as an endogenous biomarker for Oat1 activity. These findings highlight the modulatory effects of calcitriol on Oat-mediated transport and demonstrate the utility of taurine and PDA as translational biomarkers for investigating transporter-mediated drug-drug interactions in drug development.

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