title: Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin.
abstract: Berberine, the main active component of the herbal medicine Rhizoma Coptidis, has been reported to have hypoglycemic and insulin-sensitizing effects and, therefore, could be combined with metformin therapy. Thus, we assessed the potential drug-drug interactions between berberine and metformin. We investigated the in vitro inhibitory potency of berberine on metformin uptake in HEK293 cells overexpressing organic cation transporter (OCT) 1 and 2. To investigate whether this inhibitory effect of berberine on OCT1 and OCT2 could change the pharmacokinetics of metformin in vivo, we measured the effect of berberine co-administration on the pharmacokinetics of metformin at a single intravenous dose of 2 mg/kg metformin and 10 mg/kg berberine. In HEK293 cells, berberine inhibited OCT1- and OCT2-mediated metformin uptake in a concentration dependent manner and IC50 values for OCT1 and OCT2 were 7.28 and 11.3 μM, respectively. Co-administration of berberine increased the initial plasma concentration and AUC of metformin and decreased systemic clearance and volume of distribution of metformin in rats, suggesting that berberine inhibited disposition of metformin, which is governed by OCT1 and OCT2. Berberine inhibited the transport activity of OCT1 and OCT2 and showed significant potential drug-drug interactions with metformin in in vivo rats.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Dae-gu, 702-701, Korea.
authors.forename: Mihwa
authors.initials: M
authors.lastname: Kwon
authors.forename: Young A
authors.initials: YA
authors.lastname: Choi
authors.forename: Min-Koo
authors.initials: MK
authors.lastname: Choi
authors.forename: Im-Sook
authors.initials: IS
authors.lastname: Song
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001599:Berberine / Q000008:administration & dosage / Q000097:blood*; D050482:Catecholamine Plasma Membrane Transport Proteins / Q000502:physiology*; D004347:Drug Interactions / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000097:blood*; D027701:Organic Cation Transport Proteins / Q000502:physiology*; D000075102:Organic Cation Transporter 2; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D050482:Catecholamine Plasma Membrane Transport Proteins; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; C493212:Slc22a1 protein, rat; C100590:Slc22a2 protein, rat; D001599:Berberine; D008687:Metformin