PT - JOURNAL ARTICLE AU - AnHye Kim AU - Inbum Chung AU - Seo Hyun Yoon AU - Kyung-Sang Yu AU - Kyoung Soo Lim AU - Joo-Youn Cho AU - Howard Lee AU - In-Jin Jang AU - Jae Yong Chung TI - Effects of Proton Pump Inhibitors on Metformin Pharmacokinetics and Pharmacodynamics AID - 10.1124/dmd.113.055616 DP - 2014 Jul 01 TA - Drug Metabolism and Disposition PG - 1174--1179 VI - 42 IP - 7 4099 - http://dmd.aspetjournals.org/content/42/7/1174.short 4100 - http://dmd.aspetjournals.org/content/42/7/1174.full SO - Drug Metab Dispos2014 Jul 01; 42 AB - As inhibitors of organic cation transporters (OCTs), proton pump inhibitors (PPIs) may affect the plasma levels of metformin, an OCT substrate. We investigated the effects of two PPIs, pantoprazole and rabeprazole, on metformin pharmacokinetics and glucose levels in healthy subjects. In this open, randomized, six-sequence, three-period crossover study, 24 participants were administered metformin, either alone or in combination with pantoprazole or rabeprazole. The plasma concentrations of metformin and serum concentrations of glucose after a 75-g oral glucose tolerance test (OGTT) were determined. The area under the concentration-time curve (AUC) for metformin was 15% and 16% greater following coadministration with pantoprazole and rabeprazole, respectively. The maximum plasma metformin concentrations (Cmax) also increased by 15% and 22%, respectively, compared with when it was administered without the PPIs. The percentage change in the AUC for glucose concentration versus time for metformin plus rabeprazole was significantly lower than that for metformin plus pantoprazole [geometric mean ratio: 0.96 (90% confidence interval: 0.92–0.99) and 0.77 (0.63–0.93), respectively]. There was no significant difference in the maximum glucose concentration. In conclusion, concomitant administration of PPIs with metformin significantly increased plasma metformin exposure, but the effects on glucose disposition were minor and varied depending on the PPI administered.