Concentrations of trovafloxacin in colonic tissue and peritoneal fluid after intravenous infusion of the prodrug alatrofloxacin in patients undergoing colorectal surgery

BACKGROUND: Trovafloxacin is a new fourth-generation fluoroquinolone whose pharmacokinetics and in vitro activity suggest that it is well suited for antibiotic prophylaxis in elective colorectal surgery. Alatrofloxacin is a prodrug that is rapidly hydrolyzed to trovafloxacin in the body. METHODS: Twelve patients received a single dose of alatrofloxacin equivalent to 200 mg trovafloxacin by intravenous infusion over 1 hour. Surgery was started at various time points relative to infusion time to allow determination of trovafloxacin concentrations in serum, colonic tissue, and peritoneal fluid as a function of time. RESULTS: The concentration in the earliest colonic tissue sample (1.4 hours after dosing) was 1.4 μg/g. The maximum colonic tissue concentration was 2.8 μg/g in a sample taken 2 hours after dosing. Colonic tissue/serum concentration ratios in samples taken 2-10 hours after the end of infusion ranged from 0.8 to 1.47. Concentrations of trovafloxacin in peritoneal fluid ranged from below the level of quantitation to 2.1 μg/mL at the time of colonic tissue sampling and from below the level of quantitation to 2.5 μg/mL at the time of wound closure. Alatrofloxacin was well tolerated. CONCLUSIONS: After a single intravenous dose of alatrofloxacin equivalent to 200 mg trovafloxacin, trovafloxacin is distributed rapidly into colonic tissue and peritoneal fluids. Tissue concentrations approximate serum concentrations and decline in parallel for up to 10 hours after dosing.