EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS 2003, Vol.28, No.2, pp. 129-136 Bioequivalence evaluation of three different oral formulations of ciprofloxacin in healthy volunteers MANUELA T. MAYA 1 , NUNO J. GONCALVES2, NUNO E. SILVA2, AUGUSTO E. FILIPE3 , and JOSE A. MORAIS2 1 Centro de Metabolismos e Genetics; Faculdade de Fetmecie da Universidade de Lisboe, Portugal 2 Faculdade de Fermscie da Universidade de Lisboa (FFUL), Portugal 3 Tecnimede, Sociedade Tecnico-Medicinel S.A. Lisboa, Portugal Received for publication: December 5,2002 Keywords: Ciprofloxacin, human pharmacokinetics, bioavailability, bioequivalence SUMMARY Two bioequivalence studies were performed in twenty four healthy male volunteers with the objective of comparing the bioavailability of three different oral formulations of ciprofloxacin as immediate release tablets 2S0, SOO and 7S0 mg (test formulations) with a reference formulation at SOO and 7S0 mg strengths forms. In study 1, the subjects were enrolled in a single-dose, open-label, 3-period, crossover randomised study, designed to compare the bioavailability of two test formulations of ciprofloxacin (A and B) as 2S0 and SOO mg tablets, compared to the reference formulation (C), as SOO mg tablets. In study 2, the same 24-subjects were included in a single-dose, open-label, 2-period, crossover randomised study, designed to compare the bioavailability of one test formulation of ciprofloxacin (A) as compared to the reference formulation (B), both products as 7S0 mg tablets. In both studies multiple blood samples were collected over 24 hours post-dosing. One washout period of six days was observed between the periods. Plasma was harvested and assayed for ciprofloxacin using a selective and sensitive high-performance liquid chromatography (HPLC) method with UV detection. The pharmacokinetic parameter values of C max and t max were obtained directly from plasma data, k e was estimated by log-linear regression, and AUC was calculated by trapezoidal rule. Different statistical tests were performed on the basis of untransformed and log-transformed data and the overall residual variance from ANOVA. Assuming the accepted tolerance intervals, a ｾＭ･ｲｲｯｲ of 20 % and 90 % confidence intervals (a= 0.10) of all the generally accepted tests (Westlake, Schuirmann test and Wilcoxon-Tukey nonparametric tests) showed that the formulations can be considered as bioequivalent with respect to the extent of absorption, given by the AUCa-oo and with respect to rate of absorption as assessed by C max and t max . INTRODUCTION Ciprofloxacin [1-cyclopropyl-6-fluoro-l ,4-dihydro- 4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid] is Please sendreprintrequests to: to Dra Manuela T. Maya, Centro de Metabolismos e Genetica, Faculdade de Farrnacia da Universidade de Lisboa, Av. Forcas Armadas, 1600 Lisboa, Portugal a fluoroquinolone with a high level of antimicrobial activity. Ciprofloxacin is highly active in vitro against a broad spectrum ofgram-negative and gram-positive organisms, including those resistant to aminoglycosides and ｾＭｬ｡･ｴ｡ｭ antibiotics (1). Because of its wide antibacterial spectrum, ciprofloxacin has a wellestablishedrole as an antimicrobial agent. In comparison with nonfluorinated quinolones,