Pharmacokinetics and bioequivalence evaluation of two simvastatin 40 mg tablets (Simvast and Zocor) in healthy human volunteers

Biopharm Drug Dispos. 2003 Jul;24(5):183-9. doi: 10.1002/bdd.347.

Abstract

The pharmacokinetics of two brands of simvastatin 40 mg tablets were compared in 24 healthy human volunteers after a single oral dose in a randomized cross-over study, conducted at IPRC, Amman, Jordan. Reference (Zocor, MSD, Netherlands) and test (Simvast, Julphar, UAE) products were administered to fasted volunteers; blood samples were collected at specified time intervals, plasma separated and analyzed for simvastatin and its active metabolite (beta-hydoxy acid) using a validated LC-MS/MS method at Cartesius Analytical Unit, Institute of Biomedical Sciences - USP, Sao Paulo, Brazil. The pharmacokinetic parameters AUC(0-t), AUC(0-variant), C(MAX), T(MAX), T(1/2) and elimination rate constant were determined from plasma concentration-time profile for both formulations and were compared statistically to evaluate bioequivalence between the two brands, using the statistical modules recommended by FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range for bioequivalence. Based on these statistical inferences it was concluded that the two brands exhibited comparable pharmacokinetic profiles and that Julphar's Simvast is bioequivalent to Zocor of MSD, Netherlands.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid
  • Cross-Over Studies
  • Half-Life
  • Humans
  • Hypolipidemic Agents / administration & dosage
  • Hypolipidemic Agents / blood
  • Hypolipidemic Agents / pharmacokinetics*
  • Liver / enzymology
  • Liver / metabolism
  • Male
  • Mass Spectrometry
  • Simvastatin / administration & dosage
  • Simvastatin / analogs & derivatives
  • Simvastatin / blood
  • Simvastatin / metabolism
  • Simvastatin / pharmacokinetics*
  • Therapeutic Equivalency
  • Time Factors

Substances

  • Hypolipidemic Agents
  • beta-hydroxy simvastatin acid
  • Simvastatin