International Journal of Antimicrobial Agents 27 (2006) 7–14 Pharmacokinetics of ciprofloxacin XR (1000 mg) versus levofloxacin (500 mg) in plasma and urine of male and female healthy volunteers receiving a single oral dose Florian M.E. Wagenlehner a,∗ , Martina Kinzig-Schippers b , Uwe Tischmeyer a , Christine Wagenlehner a , Fritz S ¨ orgel b,c , Axel Dalhoff d , Kurt G. Naber a a Department of Urology, St Elisabeth Hospital, Straubing, Germany b Institute for Biomedical and Pharmaceutical Research (IBMP), N¨ urnberg-Heroldsberg, Germany c Department of Pharmacology, University of Essen, Germany d Bayer Research Centre, Wuppertal, Germany Received 7 July 2005; accepted 14 September 2005 Abstract The new extended-release formulation of ciprofloxacin (ciprofloxacin XR) was designed for once-daily administration in the treatment of urinary tract infection (UTI). The aim of this study was to compare concentrations in plasma, urinary excretion (UE) and pharmacokinetic parameters of ciprofloxacin XR (1000 mg) versus those of levofloxacin (500 mg) in healthy volunteers receiving a single oral dose. In this randomised crossover study, 12 volunteers (6 males, 6 females) received a single oral dose of 1000 mg ciprofloxacin XR or 500 mg levofloxacin to assess the concentrations (by high-pressure liquid chromatography) in plasma up to 32 h and the UE at intervals up to 36 h. The following pharmacokinetic parameters were studied: C max , t max , t 1/2 , AUC plasma 0→∞ , AUC plasma 0→last , Cl ren , maximal urinary concentration (U max ), AUC urine 0→last and UE. Both fluoroquinolones were well tolerated. The plasma concentrations of levofloxacin were significantly higher than those of ciprofloxacin XR throughout the study period. The urinary concentrations of ciprofloxacin XR were significantly higher than those of levofloxacin in the first collection interval (0–4h), whereas the concentrations of levofloxacin were significantly higher than those of ciprofloxacin XR in the five last collection intervals (12–36 h). The median proportions of cumulative renal excretion of the administered dose of the parent drug up to 36 h were 43.1% for ciprofloxacin XR (range, 13.7–50.8%; mean ± standard deviation (S.D.), 40.5 ± 9.9%) and 79.8% for levofloxacin (range, 74.0–88.2%; mean ± S.D., 80.4 ± 5.5%). C max , AUC plasma 0→∞ , AUC plasma 0→last and UE were statistically significantly higher in the levofloxacin than in the ciprofloxacin XR phase; t max , Cl ren and U max were statistically significantly higher in the ciprofloxacin XR phase than in the levofloxacin phase; and AUC urine 0→last and t 1/2 were not statistically different. After an oral administration of ciprofloxacin XR 1000 mg and levofloxacin 500 mg, C max and AUC plasma 0→∞ were significantly higher in the levofloxacin phase. UE of ciprofloxacin XR 1000 mg once daily, however, was equivalent to that of levofloxacin 500 mg, and overall comparable urinary concentrations and AUC urine were reached by both drugs. Therefore, it can be assumed that the two doses investigated can be considered equivalent for the treatment of UTI. © 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Urinary tract infections; Ciprofloxacin XR; Levofloxacin; Plasma and urine concentrations; Pharmacokinetic parameters 1. Introduction The fluoroquinolones are well-established broad-spect- rum antibiotics with activity against clinically important ∗ Corresponding author. Tel.: +49 9421 710 6702; fax: +49 9421 710 1717. E-mail address: Wagenlehner@AOL.com (F.M.E. Wagenlehner). uropathogens [1–4]. Fluoroquinolones are frequently used in the management of uncomplicated urinary tract infections (UTIs) [5–7]. Resistance rates of fluoroquinolones are still favourable in uncomplicated UTIs [8,9]. However, in com- plicated and nosocomial UTIs resistance rates are increasing [2,3,10–13]. Until recently, oral ciprofloxacin has been avail- able only as conventional, immediate-release tablets that 0924-8579/$ – see front matter © 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2005.09.014