Food effect on bioavailability of modified-release trimetazidine tablets

J Clin Pharmacol. 2012 Oct;52(10):1535-9. doi: 10.1177/0091270011422813. Epub 2011 Dec 12.

Abstract

This study aimed to investigate a food effect on the bio-availability of modified-release (MR) trimetazidine tablets in 36 healthy volunteers. Trimetazidine, an anti-ischemic drug, protects the myocardial cell from the harmful effects of ischemia. The authors investigated the effect of being under a fasting or fed state at the time of drug intake on the bioavailability of trimetazidine 35-mg MR tablets in a randomized, open-label, crossover, 2-arm, 4-period, 2-sequence bioequivalence study design with a 14-day washout period. Plasma concentration of trimetazidine was assayed in timed samples with a validated high- performance liquid chromatography/mass selective detector that had a lower limit of quantification of 2.5 ng/mL. Test and reference formulations gave a mean trimetazidine C(max) of 63.26 ng/mL and 69.18 ng/mL for the fasting state and 64.19 ng/mL and 63.11 ng/mL for the fed state, respectively. The AUC(0-tlast) mean of trimetazidine was 726.31 ng·h/mL and 733.01 ng·h/mL for the fasting state and 706.40 ng·h/mL and 691.40 ng·h/mL for the fed state for test/reference formulations. There were no significant differences in pharmacokinetic parameters between the 2 formulations and the fasting/fed states. The authors showed that there is no food effect and no need for a 4-period study to evaluate the bioequivalence of trimetazidine MR tablets.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biological Availability
  • Breakfast
  • Cross-Over Studies
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / pharmacokinetics
  • Fasting / metabolism
  • Food-Drug Interactions*
  • Humans
  • Male
  • Tablets
  • Therapeutic Equivalency
  • Trimetazidine / administration & dosage
  • Trimetazidine / blood
  • Trimetazidine / pharmacokinetics*
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / blood
  • Vasodilator Agents / pharmacokinetics*
  • Young Adult

Substances

  • Delayed-Action Preparations
  • Tablets
  • Vasodilator Agents
  • Trimetazidine