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.
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.
Filipe
Augusto
A
Medical Department, Grupo Tecnimede, Prior Velho, Portugal. dmed.ct.tecnimede@mail.telepac.pt
Almeida
Susana
S
Spínola
Ana Cristina Franco
AC
Trabelsi
Fethi
F
Ortuño
Jordi
J
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*
D000970:Antineoplastic Agents; D009570:Nitriles; D013607:Tablets; D014230:Triazoles; D000077289:Letrozole; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6