title: The effect of lansoprazole, an OCT inhibitor, on metformin pharmacokinetics in healthy subjects.
abstract: OBJECTIVE
  Gastro-esophageal reflux disease is common in patients with type 2 diabetes. A common treatment is the co-administration of proton-pump inhibitors (PPIs) and metformin. To date, however, the effects of co-administration of PPIs, which inhibit organic cation transporter (OCT) activity, on the action of metformin (a well-known substrate of OCTs) have not been clearly demonstrated.
  
  
  METHODS
  This was a randomized, double-blind, two-way crossover, placebo-controlled trial. Healthy male volunteers (n = 20) received metformin (single dose 1,000 mg on day 1 and single dose 750 mg on day 2, with a 12-h interval) co-administered with placebo or with lansoprazole (30 mg). Plasma concentrations of metformin were measured up to 24 h after the second dose. The glucose-lowering effects of metformin were evaluated by the oral glucose tolerance test before and after each single dose of metformin within the 2-day period.
  
  
  RESULTS
  Lansoprazole increased the mean metformin maximum plasma concentration and area under the plasma concentration-time curve from zero to 24 h after the second dosing by 15 and 17 %, respectively (P < 0.05). Moreover, lansoprazole prolonged the metformin elimination half-life from 3.9 to 4.5 h and decreased its renal clearance by 13 % (P < 0.05). However, lansoprazole had no effect on the maximum glucose level and the area under the serum glucose concentration-time curve of metformin.
  
  
  CONCLUSIONS
  Collectively, we found a modest pharmacokinetic drug interaction between lansoprazole and metformin, which suggests that the concomitant use of these drugs should be appropriately monitored. Further studies are warranted to assess changes in metformin pharmacokinetics in patients with diabetes receiving long-term lansoprazole therapy.
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: YanYan
authors.initials: Y
authors.lastname: Jia
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: ChengTao
authors.initials: C
authors.lastname: Lu
authors.forename: YuWen
authors.initials: Y
authors.lastname: Li
authors.forename: MinChun
authors.initials: M
authors.lastname: Chen
authors.forename: MingMing
authors.initials: M
authors.lastname: Wang
authors.forename: AiDong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D005951:Glucose Tolerance Test; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000652:urine; D064747:Lansoprazole / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000652:urine; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors*; D054328:Proton Pump Inhibitors / Q000494:pharmacology*
chemical_list: D000897:Anti-Ulcer Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D027701:Organic Cation Transport Proteins; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D008687:Metformin