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Competitive Inhibition of p-Aminohippurate Transport by Quinapril in Rabbit Renal Basolateral Membrane Vesicles

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Abstract

The mechanism of quinapril's interaction with the organic anion transporter was characterized by studying its effect on the transport of p-aminohippurate (PAH) in rabbit renal basolateral membrane vesicles (BLMV). Cis-inhibition studies demonstrated that quinapril was a specific and potent inhibitor of PAH. The Ki of quinapril was about 20 μM, a value similar to that of probenecid and eight-times lower than the Km value of 165 μM for PAH. Even though quinapril resulted in trans-inhibition of PAH uptake during counterflow studies, kinetic studies revealed that quinapril was a competitive inhibitor of PAH transport. This latter finding suggests that quinapril and PAH share a common binding site on the transporter. Overall, the results indicate that quinapril is a high-affinity inhibitor of the organic anion transporter in renal BLMV, and that drug–drug interactions may occur with other organic anions at the basolateral membrane of proximal cells.

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  1. College of Pharmacy and Upjohn Center for Clinical Pharmacology, The University of Michigan, Ann Arbor, 1310 E. Catherine Street, Michigan, 48109–0504

    Wiyada Akarawut & David E. Smith

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  1. Wiyada Akarawut
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Akarawut, W., Smith, D.E. Competitive Inhibition of p-Aminohippurate Transport by Quinapril in Rabbit Renal Basolateral Membrane Vesicles. J Pharmacokinet Pharmacodyn 26, 269–287 (1998). https://doi.org/10.1023/A:1023281325479

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