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Lack of interaction between the peptidomimetic substrates captopril and cephradine.

Author(s): Foster DR, Yee S, Bleske BE, Carver PL, Shea MJ, Menon SS, Ramachandran C, Welage LS, Amidon GL

Affiliation(s): Department of Pharmaceutical Sciences, Purde University School of Pharmacy and Pharmaceutical Sciences, Indianapolish, IN, USA.

Publication date & source: 2009-03, J Clin Pharmacol., 49(3):360-7.

Publication type: Clinical Trial; Randomized Controlled Trial

Intestinal peptide transporters, including hPEPT1, facilitate the absorption of cephalosporins and angiotensin-converting enzyme inhibitors, and have been investigated as a means to improve oral drug absorption. Renal peptide transporters including hPEPT2, may also facilitate renal reabsorption of such compounds. In vitro and animal studies suggest that co-administration of peptidomimetic compounds may alter oral pharmacokinetics, although this has not been well studied in humans. The purpose of this study was to determine whether co-administration of the hPEPT substrates captopril and cephradine alters the oral pharmacokinetics of either agent. Nine healthy male volunteers received a single oral 25-mg dose of captopril, a single oral 500-mg dose of cephradine, or concurrent ingestion of captopril and cephradine in a cross-over manner. Venous blood samples were taken and captopril and cephradine pharmacokinetics were determined using noncompartmental analyses. No significant differences were observed in captopril or cephradine pharmacokinetics when administered together as compared to each agent alone (a marginal decrease in C(max) was observed for both captopril and cephradine during co-administration [5-15%]; however, differences were not statistically significant). The results of our study suggest that hPEPT1 and hPEPT2 are unlikely to contribute to clinically important drug interactions in humans.

Page last updated: 2009-10-20

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