Pharmacokinetics and bioequivalence of 0.5 mg lobeglitazone tablets in healthy male subjects

Int J Clin Pharmacol Ther. 2018 Sep;56(9):426-433. doi: 10.5414/CP203134.

Abstract

Objective: This study was conducted to evaluate the pharmacokinetics and bioequivalence of two formulations of -DuvieTM (0.5-mg lobeglitazone sulfate).

Materials and methods: This study was designed as an open-label, randomized, single-dose, crossover bioequivalence study in healthy male subjects. A total of 28 subjects were randomized into two groups: one group received the test drug, 0.5-mg DuvieTM tablets, which have formulations available on the global market; and the other group received the reference drug, the initially-approved 0.5-mg DuvieTM tablets. Plasma samples were collected for up to 48 hours after drug treatment and were analyzed for lobeglitazone using validated liquid chromatography-tandem mass spectrometry. Individual pharmacokinetic properties were determined by noncompartmental methods. Safety assessments were performed.

Results: 28 subjects completed the study and were included in the pharmacokinetic analysis. The mean (standard deviation) values of -AUClast for the test and reference formulations were 367.49 (157.92) and 362.40 (140.05) ng×h/mL, respectively. The mean (standard deviation) values of Cmax for the test and reference formulations were 50.35 (6.94) and 49.29 (6.71) ng/mL, respectively. The 90% confidence intervals for AUClast and Cmax were 0.9150 - 1.1088 and 0.9879 - 1.0561, respectively. All adverse events were mild, and there were no serious adverse events.

Conclusion: This study suggests that the two lobeglitazone tablet formulations have similar exposure and absorption rates. Therefore, the newly-developed formulation of the 0.5-mg DuvieTM tablet is expected to contribute to the treatment of patients with type 2 diabetes. .

Publication types

  • Equivalence Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Drug Compounding
  • Half-Life
  • Healthy Volunteers
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics*
  • Male
  • Metabolic Clearance Rate
  • Models, Biological
  • Pyrimidines / administration & dosage*
  • Pyrimidines / blood
  • Pyrimidines / pharmacokinetics*
  • Republic of Korea
  • Spectrometry, Mass, Electrospray Ionization
  • Tablets
  • Tandem Mass Spectrometry
  • Therapeutic Equivalency
  • Thiazolidinediones / administration & dosage*
  • Thiazolidinediones / blood
  • Thiazolidinediones / pharmacokinetics*
  • Young Adult

Substances

  • Hypoglycemic Agents
  • Pyrimidines
  • Tablets
  • Thiazolidinediones
  • lobeglitazone