title: Effect of gastric bypass surgery on the absorption and bioavailability of metformin.
abstract: OBJECTIVE
  Use of gastric bypass surgery is common and increasing. Over 40% of patients in diabetes remission after gastric bypass surgery may redevelop diabetes within 5 years. Metformin, the first-line drug for diabetes, has low bioavailability and slow, incomplete gastrointestinal absorption. We hypothesized that gastric bypass would further reduce the absorption and bioavailability of metformin.
  
  
  METHODS
  In a nonblinded, single-dose pharmacokinetic study, 16 nondiabetic post-gastric bypass patients and 16 sex- and BMI-matched control subjects (mean age 40 years and BMI 39.2 kg/m(2)) were administered two 500-mg metformin tablets. Plasma metformin levels were sampled at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 h. Metformin absorption, estimated by the area under the curve (AUC) of the plasma drug concentrations from time 0 to infinity (AUC(0-∞)), was the primary outcome, and metformin bioavailability, assessed by measuring 24-h urine metformin levels, was a secondary outcome.
  
  
  RESULTS
  Compared with control subjects, metformin AUC(0-∞) was increased in gastric bypass subjects by 21% (13.7 vs. 11.4 μg/mL/h; mean difference 2.3 [95% CI -1.3 to 5.9]) and bioavailability was increased by 50% (41.8 vs. 27.8%; 14.0 [4.1-23.9]). Gastric bypass patients had significantly lower AUC glucose levels over 8 h compared with control subjects (35.8 vs. 41.7 μg/mL/h; 5.9 [3.1-8.8]), but this was likely a result of differences in baseline fasting glucose and not metformin absorption.
  
  
  CONCLUSIONS
  Metformin absorption and bioavailability seem to be higher after gastric bypass, and this may have implications on dosing and toxicity risk. Studies are needed to confirm these findings and delineate potential mechanisms.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Raj S
authors.initials: RS
authors.lastname: Padwal
authors.forename: Raniah Q
authors.initials: RQ
authors.lastname: Gabr
authors.forename: Arya M
authors.initials: AM
authors.lastname: Sharma
authors.forename: Lee-Ann
authors.initials: LA
authors.lastname: Langkaas
authors.forename: Dan W
authors.initials: DW
authors.lastname: Birch
authors.forename: Shahzeer
authors.initials: S
authors.lastname: Karmali
authors.forename: Dion R
authors.initials: DR
authors.lastname: Brocks
mesh_terms: D000042:Absorption; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000601:surgery*; D005260:Female; D015390:Gastric Bypass / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008687:Metformin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008875:Middle Aged; D012008:Recurrence
chemical_list: D008687:Metformin