(1.4)--文献4生物药剂学与药物动力学.pdf

Clin Pharmacokinet DOI 10.1007/s40262-015-0346-3 ORIGINAL RESEARCH ARTICLE The Effect of Famotidine, a MATE1-Selective Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Metformin Jennifer E. Hibma1,2 • Arik A. Zur1 • Richard A. Castro1 • Matthias B. Wittwer1 • 1 1 1 1 Ron J. Keizer • Sook Wah Yee • Srijib Goswami • Sophie L. Stocker • 3 3 4 1 Xuexiang Zhang • Yong Huang • Claire M. Brett • Radojka M. Savic • Kathleen M. Giacomini1 Springer International Publishing Switzerland 2015 Abstract Results Consistent with MATE1 inhibition, famotidine Introduction Pharmacokinetic outcomes of transporter-me- administration significantly altered creatinine plasma and diated drug–drug interactions (TMDDIs) are increasingly being urine levels in opposing directions (p \0.005). Interestingly, evaluated clinically. The goal of our study was to determine the famotidine increased the estimated bioavailability of met- effects of selective inhibition of multidrug and toxin extrusion formin [cumulative amount of unchanged drug excreted in protein 1 (MATE1), using famotidine, on the pharmacokinetics urine from time zero to infinity (Ae?)/dose; p \0.005] and pharmacodynamics of metformin in healthy volunteers. without affecting its systemic exposure [area under the plasma Methods Volunteers received metformin alone or with concentration–time curve (AUC) or maximum concentration famotidine in a crossover design. As a positive control, the in plasma (Cmax)] as a result of a counteracting increase in longitudinal effects of fam