Bioequivalence of Oral Formulations of Anastrozole in Healthy Chinese Male Volunteers: A Randomized, Single-Dose, Two-Period, Two-Sequence Crossover Study

Clin Pharmacol Drug Dev. 2019 Feb;8(2):217-222. doi: 10.1002/cpdd.450. Epub 2018 Apr 16.

Abstract

Anastrozole is currently used as first-line treatment in locally advanced or metastatic breast cancer. A generic anastrozole tablet was developed to offer an alternative to the marketed tablet formulation. The aim of the current study was to evaluate the bioequivalence between the test and reference formulations of anastrozole in a single-dose, 2-period, 2-sequence crossover study with a 14-day washout interval. A total of 20 healthy male Chinese volunteers were enrolled and completed the study, after oral administration of a single dose of 1.0-mg test and reference formulations of anastrozole. The blood samples were collected at different times and were determined by a fully validated high-pressure liquid chromatography-tandem mass spectrometry method. The evaluated pharmacokinetic parameters, including Cmax , AUC0-t , and AUC0-∞ , were assessed for bioequivalence based on current guidelines. The observed pharmacokinetic parameters of anastrozole of the test drug were similar to those of the reference formulation. The 90% confidence intervals of test/reference ratios for Cmax , AUC0-t , and AUC0-∞ were within the bioequivalence acceptance range of 80%-125%. The results obtained from these healthy Chinese subjects in this study suggest that the test formulation of anastrozole 1.0-mg tablet is bioequivalent to the reference formulation (Arimidex 1.0-mg tablet).

Keywords: LC-MS/MS; anastrozole; bioequivalence; pharmacokinetics.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Anastrozole / administration & dosage*
  • Anastrozole / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • China
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Drugs, Generic / administration & dosage*
  • Drugs, Generic / pharmacokinetics*
  • Healthy Volunteers
  • Humans
  • Male
  • Tablets
  • Tandem Mass Spectrometry
  • Therapeutic Equivalency
  • Young Adult

Substances

  • Drugs, Generic
  • Tablets
  • Anastrozole