URINARY BACTERICIDAL ACTIVITY AND PHARMACOKINETICS OF ENOXACIN VERSUSNORFLOXACIN AND CIPROFLOXACIN IN HEALTHY-VOLUNTEERS AFTER A SINGLE ORAL DOSE

In an open, randomised monocentric crossover study in six male and six female healthy volunteers, the urinary antibacterial activity and pha rmacokinetics of enoxacin, norfloxacin and ciprofloxacin were assessed . Urine was collected up to 6 days, and venous blood samples up to 12 h, after a single oral dose of 400 mg enoxacin, 400 mg norfloxacin and 500 mg ciprofloxacin. Enoxacin (250 mg/l) demonstrated the highest pe ak concentration (median) in the urine (0-6 h), followed by ciprofloxa cin (237 mg/l) and norfloxacin (157 mg/l) as determined by the HPLC as say. The total amount (mean) excreted by the kidneys as parent drugs w ere as follows: enoxacin 54% of dose, ciprofloxacin 33% of dose, and n orfloxacin 22% of dose. The mean plasma concentrations decreased from 1 to 4 h after administration for enoxacin from 1.9 to 1.4 mg/l, for c iprofloxacin from 2.0 to 0.8 mg/l and for norfloxacin from 1.3 to 0.5 mg/l. The antibacterial activity in urine was determined as urinary ba ctericidal titers (UBT), i.e. the highest 2-fold dilution of urine sti ll bactericidal for the reference organism (E. coli ATCC 25922) and fo r five uropathogens with minimal inhibitory (MIC) and bactericidal (MB C) concentrations ranging from highly susceptible to resistant culture d from the urine of patients with complicated urinary tract infections (UTI). For the E. coli ATCC 25922, the organism with the lowest MIC, median UBTs of ciprofloxacin were present for 4 days, decreasing from 1:512 to 1:2, that of enoxacin for 2 days, decreasing from 1:256 to 1: 4, and that of norfloxacin for 2 days, decreasing from 1:128 to 1:2. F or the five uropathogens (with increasing MICs: K. pneumoniae, P. mira bilis, E. coil (resistant to nalidixic acid), P. aeruginosa and E. fae calis), the UBTs decreased in general, according to MICs, demonstratin g the same relations of UBTs for ciprofloxacin (highest) versus enoxac in (medium) versus norfloxacin (lowest) with one exception (P. mirabil is) for which norfloxacin showed higher UBTs than enoxacin. The minima l urinary bactericidal concentrations (MUBC), as derived from urinary concentrations, and UBTs showed a fairly wide inter- and intraindividu al range and were generally higher than the corresponding MBCs as dete rmined in Mueller Hinton broth. In conclusion, according to antibacter ial activity in urine determined as UBTs, a single oral dose of ciprof loxacin (500 mg) generally resulted in the highest and longest-lasting UBTs followed by that of enoxacin (400 mg) and norfloxacin (400 mg). A dose of 400 mg enoxacin can be expected to be at least equivalent if not superior to that of 400 mg norfloxacin. Only enoxacin and ciprofl oxacin exhibited urinary bactericidal activity against all test organi sms up to 12 h in all individuals. Therefore, clinical comparison of e noxacin versus ciprofloxacin in the treatment of complicated UTI could be worth testing. (C) 1998 Elsevier Science B.V./International Societ y of Chemotherapy. All rights reserved.