title: 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.
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.
authors.affiliation: Medical Department, Grupo Tecnimede, Prior Velho, Portugal. dmed.ct.tecnimede@mail.telepac.pt
authors.forename: Augusto
authors.initials: A
authors.lastname: Filipe
authors.forename: Susana
authors.initials: S
authors.lastname: Almeida
authors.forename: Ana Cristina Franco
authors.initials: AC
authors.lastname: Spínola
authors.forename: Fethi
authors.initials: F
authors.lastname: Trabelsi
authors.forename: Jordi
authors.initials: J
authors.lastname: Ortuño
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D065637:Cytochrome P-450 CYP2A6; D004311:Double-Blind Method; D005215:Fasting / Q000378:metabolism; D005260:Female; D006801:Humans; D000077289:Letrozole; D016014:Linear Models; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D013607:Tablets; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D013607:Tablets; D014230:Triazoles; D000077289:Letrozole; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6