title: The effects of rabeprazole on metformin pharmacokinetics and pharmacodynamics in Chinese healthy volunteers.
abstract: The aim was to investigate the role of rabeprazole on the pharmacokinetics (PK) and pharmacodynamics (PD) of metformin. The in vitro inhibition assays on metformin transport were carried out and showed that the half maximal inhibitory concentration (IC50) of rabeprazole on OCT2-mediated metformin transport was 26.0 μM, whereas the IC50on MATE1-mediated metformin transport inhibition was 4.6 μM. Fifteen healthy Chinese male volunteers were enrolled and given two different doses of metformin plus the co-administration of placebo or rabeprazole. Plasma concentrations of metformin were measured up to 12 h after the second dose. The glucose-lowering effects and the variation of insulin concentrations were evaluated during the oral glucose tolerance test (OGTT). The AUC0-12of metformin plus rabeprazole were 28,276 ± 5187 ng/ml·h, which was significantly higher than AUC0-12of metformin plus placebo (24,691 ± 3129 ng/ml·h). Thus, rabeprazole can modestly influence the PK of metformin, suggesting the precaution of using the two drugs together. In OGTTs, rabeprazole decreased the values of AUCinsulinand the maximum insulin concentration. Although rabeprazole showed inhibition effect on OCT2-mediated metformin transport, the glucose-lowering effect of metformin remained the same regardless of its PK changes. Further studies are needed to warrant the effect of rabeprazole on metformin.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China.
authors.forename: Guojing
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China.
authors.forename: Jiagen
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China.
authors.forename: Zhaoqian
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China.
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China. Electronic address: yjsd2003@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004347:Drug Interactions; D057809:HEK293 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007328:Insulin / Q000097:blood; D008297:Male; D008687:Metformin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000075102:Organic Cation Transporter 2; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D064750:Rabeprazole / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D054328:Proton Pump Inhibitors; C491013:SLC22A2 protein, human; C521869:SLC47A1 protein, human; D064750:Rabeprazole; D008687:Metformin
keywords: Metformin; Pharmacodynamics; Pharmacokinetics; Rabeprazole; Transporter