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 a ntibiotic prophylaxis in elective colorectal surgery. Alatrofloxaccin is a prodrug that is rapidly hydrolyzed to trovafloxacin in the body. METHODS: Twelve patients received a single dose of alatrofloxacin equivalen t to 200 mg trovafloxacin by intravenous infusion over 1 hour. Surgery was started at various time points relative to infusion time to allow determina tion of trovafloxacin concentrations in serum, colonic tissue, and peritone al fluid as a function of time. RESULTS: The concentration in the earliest colonic tissue sample (1.4 hours after dosing) was 1.4 mu g/g. The maximum colonic tissue concentration was 2.8 mu g/g in a sample taken 2 hours after dosing. Colonic tissue/serum co ncentration ratios in samples taken 2-10 hours after the end of infusion ra nged from 0.8 to 1.47. Concentrations of trovafloxacin in peritoneal fluid ranged from below the level of quantitation to 2.1 mu g/mL at the time of c olonic tissue sampling and from below the level of quantitation to 2.5 mu g /mL at the time of wound closure. Alatrofloxacin was well tolerated. CONCLUSIONS: After a single intravenous dose of alatrofloxacin equivalent t o 200 mg trovafloxacin, trovafloxacin is distributed rapidly into colonic t issue and peritoneal fluids. Tissue concentrations approximate serum concen trations and decline in parallel for up to 10 hours after dosing. (C) 1998 by Excerpta Medica, Inc.