Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination tablets of pioglitazone and metformin. Effect of body weight, gender, and race on systemic exposures of each drug

J Clin Pharmacol. 2007 Jan;47(1):37-47. doi: 10.1177/0091270006293755.

Abstract

Bioavailability of pioglitazone and metformin, in 2 dose strengths, given either as a fixed-dose combination tablet or as coadministration of commercial tablets (coad), was studied in young healthy subjects in 2 separate studies. In study I (n = 63), single oral doses of 15-mg pioglitazone/500-mg metformin fixed-dose combination tablets or equivalent doses of commercial tablets were administered, in a fasting state, in an open-label, randomized, crossover study with a 7-day washout period between treatments. Study II (n = 61) was similar in design to study I, except the 15/850-mg fixed-dose combination tablet and coad treatments were evaluated. Least squares mean (fixed-dose combination/coad) ratios and 90% confidence intervals of the ratios for the 15/500-mg dose strength for the maximum observed serum concentration (Cmax) and area under the serum concentration-time curve from time 0 to infinity (AUC(infinity)) were 0.95 (0.86-1.05) and 1.02 (0.98-1.08), respectively, for pioglitazone and 0.99 (0.95-1.03) and 1.03 (0.98-1.08), respectively, for metformin. Bioequivalency for pioglitazone and metformin between fixed-dose combination tablets and coad treatments was met for both strengths of fixed-dose combination tablets. In a post hoc meta-analysis of combined data from the 2 studies (n = 124), there was considerable overlapping in AUC(infinity) values between gender and race (Caucasians, Blacks, and Hispanics), making neither gender- nor racial-based dosing of pioglitazone or metformin necessary.

Publication types

  • Meta-Analysis
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Biological Availability
  • Blacks
  • Body Weight
  • Drug Combinations
  • Female
  • Hispanic or Latino
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics*
  • Least-Squares Analysis
  • Male
  • Metformin / administration & dosage
  • Metformin / blood
  • Metformin / pharmacokinetics*
  • Middle Aged
  • Pioglitazone
  • Sex Factors
  • Therapeutic Equivalency
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / blood
  • Thiazolidinediones / pharmacokinetics*
  • Whites

Substances

  • Drug Combinations
  • Hypoglycemic Agents
  • Thiazolidinediones
  • Metformin
  • Pioglitazone