Bioequivalence evaluation of two roxithromycin formulations in healthy human volunteers by high performance liquid cromatography coupled to tandem mass spectrometry

RESUMO

The bioequivalence of two different formulations containing roxithromycin (SPE-712-1). Oral suspension 300mg/ 15mL as test formulation and Rotram©, tablets 300mg as reference formulation, both by Schering Plough S.A., Brazil) was evaluated in 24 healthy volunteers of both sexes (12 male and 12 female). The study was conducted open with randomized two-period crossover design and a 14-day washout period. Each subject received 300 mg of each roxithromycin formulation. Plasma samples were obtained over a 72-hour interval and roxithromycin concentrations were analyzed by combined LC-MS/MS with positive ion electrospray ionization using selected ion monitoring method. From the plasma roxithromycin concentration vs time curves the following pharmacokinetic parameters were obtained AUC(0-72h), AUC(0-oo), Cmax,t1/2 ratios and tmax individual differences. The 90 percent for confidence interval (CI) of geometric mean SPE-712-L/ Rotram© individual percent ratio were 105.0-128,3 percent for AUC(0-72h), and 78.4-96.9 for Cmax. Although this 90 percent Cl were marginally outside the interval proposed by the Food and Drug Administration, the probability assessed by the two-one sided West for ratios was included in the 0.8-1.25 interval, as we concluded that SPE-712-L oral suspension formulation was bioequivalent to Rotram tablet formulation for the extent and rate of absorption.