Meta-analysis of steady-state pharmacokinetics of troglitazone and its metabolites

J Clin Pharmacol. 1997 Nov;37(11):1038-47. doi: 10.1002/j.1552-4604.1997.tb04285.x.

Abstract

The object of this study is to evaluate the effects of age, gender, age-by-gender interaction, Type II diabetes, body weight, race, smoking, and formulation on steady-state pharmacokinetics of troglitazone, Metabolite 1 (sulfate conjugate), and Metabolite 3 (quinone metabolite) following multiple-dose oral administration of troglitazone. Pharmacokinetic parameter estimates [Cl/F (apparent oral clearance), AUC0-24 (area under plasma concentration-time curve), and ratio of AUC for troglitazone to Metabolite 1 and to Metabolite 3] obtained from 84 healthy volunteers and 171 patients with Type II diabetes in 8 studies were analyzed using a graphical method (for race and smoking) or a weighted ANCOVA model incorporating gender, health status (healthy vs Type II diabetes), and formulation as main effects; age, age-by-gender interaction, and body weight as continuous covariates. Ratio of AUC for troglitazone to metabolites was also examined by inspection of log-probit plots. Age, gender, age-by-gender, Type II diabetes, and formulation had negligible effects on troglitazone Cl/F, AUC0-24 (all analytes), and AUC ratio of troglitazone to metabolites. Race and smoking did not appear to influence steady-state pharmacokinetics of troglitazone and its metabolites. Although body weight was a significant covariate for AUC0-24 and Cl/F, the explanatory power of the overall model was weak (R2 < 0.2). Log-probit plots did not reveal a polymorphic distribution in AUC ratio of troglitazone to Metabolite 1 or Metabolite 3. Based on pharmacokinetics, dose adjustment for troglitazone in relation to the demographic factors examined is not required due to their poor predictive ability on steady-state pharmacokinetics of troglitazone and its metabolites.

Publication types

  • Meta-Analysis

MeSH terms

  • Age Factors
  • Area Under Curve
  • Body Weight
  • Chromans / blood
  • Chromans / pharmacokinetics*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / ethnology
  • Humans
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics*
  • Sex Factors
  • Smoking
  • Thiazoles / blood
  • Thiazoles / pharmacokinetics*
  • Thiazolidinediones*
  • Troglitazone

Substances

  • Chromans
  • Hypoglycemic Agents
  • Thiazoles
  • Thiazolidinediones
  • Troglitazone