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International Journal of Clinical Pharmacology and Therapeutics, Vol. 45 – No. 6/2007 (373-376)

Bioequivalence of ciprofloxacin tablet formulations assessed in Indonesian volunteers
Original
©2007 Dustri-Verlag Dr. K. Feistle ISSN 0946-1965

Y. Harahap1, B. Prasaja2, E. Indriati2, W. Lusthom2 and Lipin2 of Pharmacy, Faculty of Mathematics and Sciences, University of Indonesia, 2ClinisindoLaboratories, Jakarta, Indonesia Bioequivalence of ciprofloxacin tablet formulations assessed in Indonesian volunteers
1Department

Key words bioequivalence – ciprofloxacin – pharmacokinetics

Abstract. Aim: Determination of the bioequivalence of two ciprofloxacin tablet formulations (test formulation manufactured by Novell Pharmaceutical Laboratories, Indonesia, reference formulation fromQuimica Farmaceutica Bayer, Spain). Subjects and methods: 24 healthy volunteers received each of the two ciprofloxacin formulations at a dose of 500 mg in a 2-way crossover design. Blood samples were obtained prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 h after drug administration. Plasma concentrations of ciprofloxacin were monitored using high-performance liquid chromatographyover a period of 24 h after administration. The pharmacokinetics parameter AUC0-24h, AUC0-¥ and Cmax were tested for bioequivalence after log-transformation of data and ratios of tmax were evaluated nonparametrically. Results: The point estimates and 90% confidence intervals for AUC0-24h, AUC0-¥ and Cmax were 97.55% (92.71 – 102.6%), 97.63% (92.90 – 102.59%) and 95.84% (89.95 – 102.10%),respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines. Conclusion: These results indicate that two medications of ciprofloxacin are bioequivalent and, thus, may be prescribed interchangeably.

cluding Pseudomonas aeruginosa. The drug is also active against some Gram-positive bacteria(Staphylococcus aureus). Ciprofloxacin shows a concentration-dependent bactericidal action [Craig 1995] and, therefore, maximal efficacy is dependent on sufficiently high plasma concentration. Ciprofloxacin is rapidly and well-absorbed after oral administration. The drug is pre-eliminated principally by urinary excretion. About 40 – 50% of an oral dose are excreted unchanged in urine with about 15% excretedas metabolites. Non-renal clearance may account for about a third of elimination (hepatic metabolism, biliary excretion and possibly transluminal secretion across intestinal mucosa). The plasma half-life is about 3.5 – 4.5 h [Moffat et al. 2004]. This study was intended to evaluate the bioequivalence of 500 mg ciprofloxacin tablet manufactured by Novell Pharmaceutical Laboratories, Indonesia, witha reference tablet manufactured by Quimica Farmaceutica Bayer, Spain.

Subjects and methods
Received October 15, 2006; accepted in revised form January 26, 2007 Correspondence to Dr. Y. Harahap, MS Department of Pharmacy, Faculty of Mathematics and Sciences, University of Indonesia, Depok 16424, Indonesia yahdiana03@ yahoo.com

Introduction
Ciprofloxacin(1-cyclopropyl-6-fluoro1,4-dihydro-4-oxo-7-piperazin-1-ylquinolin e-3-carboxylic acid) is a fluoroquinolic antibacterial agent effective in the treatment of infections of the urinary tract, lower respiratory tract, skin, bone and joints and in the treatment of sexually transmitted diseases caused by a wide range of bacteria. These are mainly Gram-negative (Enterobacteriaceae, Neisseria, Moraxella catarrhalis, Haemophilus) in-Based on a previous study about intrasubject coefficient of variation, we chose a number of 24 volunteers [Cuadrado et al. 2004, Diletti et al. 1991]. The sample size of n = 24 of subjects was sufficient to ensure a power of 80% for correctly concluding bioequivalence under the following assumptions: a = 0.05, 0.95 < mT/mR < 1.05. The subjects were of both sexes, aged between 18 and 33 years (26.1...