Bioequivalence study of two letrozole tablet formulations. Single dose, randomized, open-label, two-way crossover bioequivalence study of letrozole 2.5 mg tablets in healthy volunteers under fasting conditions

Arzneimittelforschung. 2008;58(8):419-22. doi: 10.1055/s-0031-1296530.

Abstract

The study was conducted in order to compare the bioavailability of two tablet formulations containing letrozole 2.5 mg (CAS 112809-51-5). Twenty healthy subjects were enrolled in a single-centre, bioequivalence, randomised, single-dose, open-label, two-way crossover study, performed under fasting conditions with a minimum washout period of 21 days. Plasma samples were collected up to 240 h post-dosing. Letrozole levels were determined by reverse liquid chromatography and detected by tandem mass spectrometry detection, LC/MS/MS method. Pharmacokinetic parameters used for bioequivalence assessment, area under the concentration-time curve from time zero to time of last non-zero concentration (AUC(0-t)) and from time zero to infinitive (AUC(0-inf)) and maximum observed concentration (Cmax), were determined from the letrozole concentration data using non-compartmental analysis. The 90% confidence intervals obtained by analysis of variance were 90% geometric confidence Intervals of the ratio (A/B) of least-squares means from the analysis of variance (ANOVA) of the In-transformed AUC(0-t), and Cmax was within 80% to 125%. Bloequivalence between formulations was concluded both in terms of rate and extent of absorption.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Chemistry, Pharmaceutical
  • Cross-Over Studies
  • Cytochrome P-450 CYP2A6
  • Double-Blind Method
  • Fasting / metabolism
  • Female
  • Humans
  • Letrozole
  • Linear Models
  • Middle Aged
  • Nitriles / administration & dosage*
  • Nitriles / adverse effects
  • Nitriles / pharmacokinetics*
  • Tablets
  • Triazoles / administration & dosage*
  • Triazoles / adverse effects
  • Triazoles / pharmacokinetics*

Substances

  • Antineoplastic Agents
  • Nitriles
  • Tablets
  • Triazoles
  • Letrozole
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP2A6