Two studies determined the oral bioavailability of trovafloxacin (CP-99,219) in healthy volunteers under fasted and fed conditions. In a randomized, two-way crossover study, 12 fasting subjects received two 100 mg tablets of trovafloxacin and an equivalent dose of alatrofloxacin (CP-116,517), administered by i.v. infusion over 1 h. Alatrofloxacin, the L-Ala-L-Ala prodrug of trovafloxacin, is rapidly converted in the body to trovafloxacin. After the oral dose of trovafloxacin, the mean Cmax and AUC were 2.2 mg/L and 30.4 mg x h/L, respectively. After the infusion of alatrofloxacin, the Cmax and AUC of trovafloxacin were 3.2 mg/L and 34.7 mg x h/L, respectively. The mean T(1/2) after both treatments was about 11 h. The mean Cl and Vd(ss) of trovafloxacin after the infusion of alatrofloxacin were 1.32 mL/min/kg and 1.13 L/kg, respectively. The mean oral bioavailability of trovafloxacin was estimated to be 87.6% (range 64.8-122.1%). Another randomized, open, three-way crossover study was conducted in 12 healthy male volunteers to investigate the effect of food in the gastrointestinal tract on the bioavailability of trovafloxacin. Each subject received three 100 mg tablets after fasting overnight (treatment A) or after a standard breakfast (treatment B), or 300 mg as oral aqueous suspension after fasting overnight (treatment C). Mean Tmax after treatment B occurred 2.2 h later (3.6 h vs 1.4 h) than after treatment A. Mean Cmax and AUC were 2.3 and 2.6 mg/L and 38.2 and 39.5 mg x h/L after B and A, respectively. About 5% of the administered dose was recovered unchanged in the 24 h urine sample after all three treatments. Thus, the food reduced mean Cmax by 12% but had no appreciable effect on mean AUC. The mean bioavailability of trovafloxacin administered as treatment regimen B was 96.6% relative to that of treatment A. The respective mean bioavailabilities of trovafloxacin as treatments B and A were 91.3% and 94.5% respectively of that of treatment C. The results of these studies indicate that trovafloxacin has good oral bioavailability and that the ingestion of food is unlikely to have a clinically significant effect on the bioavailability of trovafloxacin.