title: Comparative bioavailability of two formulations of terbinafine. Data from a cross-over, randomised, open-label bioequivalence study in healthy volunteers.
abstract: An open-label, randomised, cross-over single dose study, using 2 periods x 2 sequences, with a minimum washout period of 21 days, was conducted in order to assess the comparative bioavailability of two formulations of terbinafine (CAS 78628-80-5) 250 mg tablets. Plasma samples were obtained at baseline, +0.333; 0.667; 1.00; 1.33; 1.67; 2.00; 2.33; 2.67; 3.00; 3.50; 4.00; 6.00; 8.00; 12.0; 24.0; 36.0; 48.0 and 72.0 h post-administration. Terbinafine levels were determined by high pressure liquid chromatography with tandem mass detection (HPLC-MS/MS) and the lower limit of quantification was set at 9.99 ng/mL. The pharmacokinetic parameters used for the bioequivalence assessment (AUClast, AUCinf and Cmax) were determined from the terbinafine concentration data using non-compartmental analysis. Classical 90% confidence intervals (90CI) were calculated for the overall sample, and for males and females separately, and gender effects were investigated using an appropriate model. The results showed that overall classical 90CI were 96.08-105.40% for AUCinf, 95.68-105.33 for AUClast and 88.24-112.83 for Cmax, that is, all within the predefined ranges for bioequivalence acceptance. Separate gender analysis showed very similar results for males and females when analysed independently, and no gender effects were detected (p>0.05 for all of the tested model effects). It may be therefore concluded that the evaluated formulations are bioequivalent 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: Susana
authors.initials: S
authors.lastname: Almeida
authors.forename: Augusto
authors.initials: A
authors.lastname: Filipe
authors.forename: François
authors.initials: F
authors.lastname: Vallée
authors.forename: Mario
authors.initials: M
authors.lastname: Tanguay
authors.forename: Richard
authors.initials: R
authors.lastname: Larouche
authors.forename: Audrey
authors.initials: A
authors.lastname: Lainesse
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects / Q000493:pharmacokinetics*; D012727:Sex Characteristics; D000077291:Terbinafine; D013810:Therapeutic Equivalency
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D000077291:Terbinafine