title: Verapamil decreases the glucose-lowering effect of metformin in healthy volunteers.
abstract: OBJECTIVE
  The organic cation transporter 1 (OCT1) plays a key role in the cellular transport of metformin and its subsequent glucose-lowering effect. A recent non-clinical study reported that metformin uptake into hepatocytes is regulated via OCT1, and that uptake was strongly inhibited by verapamil. Therefore, we investigated the effects of verapamil co-administration on the pharmacokinetics and pharmacodynamics of metformin in humans.
  
  
  METHODS
  We evaluated the pharmacokinetics and the anti-hyperglycaemic effects of metformin using an oral glucose tolerance test (OGTT) in 12 healthy participants, before (day 1) and after metformin treatment (day 2), and again on days 15 and 16 after co-administration with verapamil.
  
  
  RESULTS
  Verapamil inhibited the ability of metformin to reduce maximum blood glucose concentrations (ΔGmax ) by 62.5% (P = 0.008) and decreased the area under the glucose concentration-time curve (ΔAUCgluc ) by 238% (P = 0.015). However, verapamil did not significantly alter the Cmax and the AUC of metformin, nor its renal clearance.
  
  
  CONCLUSIONS
  Our results suggest that verapamil remarkably decreases the glucose-lowering effect of metformin, possibly by acting as a competitive inhibitor of OCT1.
authors: Department of Pharmacology, Yonsei University College of Medicine, Seoul; Brain Korea 21 Project for Medical Science, Yonsei University, Seoul.
authors: Sung Kweon
authors: SK
authors: Cho
authors: Choon Ok
authors: CO
authors: Kim
authors: Eun Seok
authors: ES
authors: Park
authors: Jae-Yong
authors: JY
authors: Chung
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004347:Drug Interactions; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000493:pharmacokinetics / Q000494:pharmacology*; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors; D027702:Organic Cation Transporter 1 / Q000037:antagonists & inhibitors; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; C521869:SLC47A1 protein, human; D008687:Metformin; D014700:Verapamil
keywords: OCT1; drug interaction; metformin; verapamil