Urinary Bactericidal Activity of Extended-Release Ciprofloxacin (1,000 Milligrams) versus Levofloxacin (500 Milligrams) in Healthy Volunteers Receiving a Single Oral Dose

Abstract

Twelve volunteers received a single oral dose of 1,000 mg extended-release (XR) ciprofloxacin versus 500 mg levofloxacin to assess urinary bactericidal titers (UBTs) against common uropathogens. Areas under UBT-time curves were significantly larger for Proteus mirabilis with XR ciprofloxacin and for staphylococci with levofloxacin.Complicated urinary tract infections (UTIs) are caused by gram-negative and -positive uropathogens (25). Fluoroquinolones are among the drugs of choice for empirical antibiotic therapy. They differ, however, in pharmacokinetic properties (11) and in antibacterial activity, and their antibacterial activity in urine is reduced significantly depending on urine pH and contents (6, 15). Extended-release (XR) ciprofloxacin and levofloxacin are given once daily (12,23). The purpose of this study was to compare the ex vivo pharmacokinetic/pharmacodynamic properties, including urinary bactericidal titers (UBTs) of a single oral dose of 1,000 mg extended-release ciprofloxacin versus 500 mg levofloxacin against common uropathogens. The pharmacokinetic aspects of this study were recently published (24).Twelve healthy volunteers successively received one oral dose of 1,000 mg extended-release ciprofloxacin (Bayer Vital GmbH, Wuppertal, Germany) or 500 mg levofloxacin (SanofiAventis, Berlin, Germany) in a crossover design at an interval of 7 days according to the randomization schedule. All voided urine samples were collected over a 12-h interval prior to drug administration (to obtain antibiotic-free urine from each individual) and at the following time intervals after administration of the drug: 0 to 4, 4 to 8, 8 to 12, 12 to 16, 16 to 24, 24 to 28, 28 to 32, and 32 to 36 h. All samples were stored at Ϫ20°C. Levofloxacin and ciprofloxacin were analyzed in one chromatographic run by high-pressure liquid chromatography. The drug concentrations in serum and urine samples were measured by comparison with a serum and urine calibration row, respectively (24). MICs, minimal bactericidal concentrations (MBCs), and urinary bactericidal titers were determined as published previously (17,26).The bacterial strains used in this study and ciprofloxacin and levofloxacin MICs are depicted in Table 1. The MBCs of levofloxacin and ciprofloxacin were similar to the corresponding MICs for all strains tested. The area under the 24-h UBTversus-time curve (AUBC) (13) was calculated as the sum of the reciprocal UBT values and the respective time intervals for each test organism and for each drug. Laboratory, UBT, and AUBC data for the two drugs were compared for each individual by the paired t test. The application of the paired t test appears adequate according to our previous analysis of the respective residuals (16). An ␣ value of 0.05 was determined to be statistically significant. Due to the high number of tests performed, the results are of descriptive nature only. The clinical significance of the statistical results, however, should be evaluated. Statistical calculations were performed using the Microsoft Excel 97...

Urinary Concentrations and Antibacterial Activities of Nitroxoline at 250 Milligrams versus Trimethoprim at 200 Milligrams against Uropathogens in Healthy Volunteers

“…UBTs have been shown to serve as valuable pharmacokinetic/pharmacodynamic parameters predicting urinary antibacterial efficacy in the assessment of fluoroquinolones (28,(31)(32)(33). In a study with patients with complicated UTIs, the UBT and AUBT 24 values for levofloxacin were highly correlated with clinical and/or microbiological success or failure (34).…”

“…In order to integrate pharmacokinetic and pharmacodynamic parameters, the urinary inhibitory titers (UITs), urinary bactericidal titers (UBTs), and urinary bactericidal kinetics (UBK) for common uropathogens were determined after oral administration of recommended therapeutic doses of 250 mg NTX and 200 mg TMP (26)(27)(28). NTX is excreted in the urine in unconjugated as well as conjugated (e.g., glucuronide and sulfate) forms (29,30).…”

Urinary Pharmacokinetics and Bactericidal Activity of Finafloxacin (200 and 800 mg) in Healthy Volunteers Receiving a Single Oral Dose

“…Higher urinary concentrations of magnesium, which are commonly in the range of 8–10 m M , in combination with a low pH value account in large part for this reduction in activity [7,22,23]. For the treatment of UTI, the bactericidal activity of an antibacterial agent measured in urine is therefore considered to be a helpful pharmacodynamic parameter [16,17,30] that has also been shown to be accurate and reproducible [31]. The urine AUC/minimal bactericidal concentration (MBC) ratio relates directly to the AUBT because the reciprocal UBT indicate the urinary concentrations divided by the MBC as determined in urine.…”

Bioequivalence of Two Oral Extended Release Formulations of Ciprofloxacin Tablets in HealthyMale Volunteers under Fed and Fasting Conditions

“…[8,12,15,19,14]. [18] showed that ciprofloxacin XR possessed larger AUCs than levofloxacin. Patients' compliance improvement using ciprofloxacin XR and thus decrease the risk of treatment failure and the spread of antibiotic resistance are also reported [17].…”