title: Comparative bioavailability of two formulations of levofloxacin and effect of sex on bioequivalence analysis. Data from a randomised, 2 x 2 crossover trial in healthy volunteers.
abstract: Bioequivalence of levofloxacin (CAS 100986-85-4) 500 mg tablets was assessed in a single dose, open, randomised, crossover trial, with a minimum washout period of 7 days. Serum samples were obtained over 36 h (at baseline, 0.250, 0.500, 0.750, 1.00, 1.25, 1.50, 1.75, 2.00, 2.33, 2.67, 3.00, 4.00, 6.00, 8.00, 12.0, 16.0, 24.0, and 36.0 h post-dose). Levofloxacin serum concentration levels were determined by high-pressure liquid chromatography with fluorescence detection (LOQ 98.31 ng/mL). The 90% confidence intervals (90% Cls; obtained by ANOVA using In-transformed data) for overall bioequivalence analysis were 99.09-115.26% for Cmax, 99.41-105.60% for AUClast and 98.68-104.93% for AUCinf, that is, all within the predefined ranges. Within-gender analysis also produced 90% CIs within the predefined ranges. The use of gender-related model effects showed that sex was a significant factor for AUClast and AUCinf, however, when parameters were normalised by body weight adjusted dose, none of the tested model effects were significant. Comparison between male and female body weight showed significant differences. It may be therefore concluded that the evaluated formulations are bioequivalent in terms of rate and extent of absorption and that possible differences between male and female pharmacokinetic parameters may be related to differences in body weight.
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: Ana
authors.initials: A
authors.lastname: Almeida
authors.forename: Hon
authors.initials: H
authors.lastname: Wong
authors.forename: Natalia
authors.initials: N
authors.lastname: Caparrós
authors.forename: Mario
authors.initials: M
authors.lastname: Tanguay
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001835:Body Weight / Q000502:physiology; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012727:Sex Characteristics; D013810:Therapeutic Equivalency
chemical_list: D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin