ORAL BIOAVAILABILITY OF TROVAFLOXACIN WITH AND WITHOUT FOOD IN HEALTHY-VOLUNTEERS

Two studies determined the oral bioavailability of trovafloxacin (CP-9 9,219) in healthy volunteers under fasted and fed conditions. In a ran domized, 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 iv infusion over 1 h. Alatrofloxacin, th e L-Ala-L-Ala prodrug of trovafloxacin, is rapidly converted in the bo dy to trovafloxacin. After the oral dose of trovafloxacin, the mean C- max and AUC were 2.2 mg/L and 30.4 mg.h/L, respectively. After the inf usion of alatrofloxacin, the C-max and AUC of trovafloxacin were 3.2 m g/L and 34.7 mg.h/L, respectively. The mean T-1/2 after both treatment s was about 11 h. The mean CI and Vd(SS) of trovafloxacin after the in fusion of alatrofloxacin were 1.32 ml/min/kg and 1.13 L/kg, respective ly. The mean oral bioavailability of trovafloxacin was estimated to be 87.6% (range 64.8-122.1%). Another randomized, open, three-way crosso ver study was conducted in 12 healthy male volunteers to investigate t he effect of food in the gastrointestinal tract on the bioavailability of trovafloxacin. Each subject received three 100 mg tablets after fa sting overnight (treatment A) or after a standard breakfast (treatment B), or 300 mg as oral aqueous suspension after fasting overnight (tre atment C). Mean T-max after treatment B occurred 2.2 h later (3.6 h vs 1.4 h) than after treatment A. Mean C-max and AUC were 2.3 and 2.6 mg /L and 38.2 and 39.5 mg.h/L after B and A, respectively. About 5% of t he administered dose was recovered unchanged in the 24 h urine sample after all three treatments. Thus, the food reduced mean C-max by 12% b ut had no appreciable effect on mean AUC. The mean bioavailability of trovafloxacin administered as treatment regimen B was 96.6% relative t o that of treatment A. The respective mean bioavailabilities of trovaf loxacin as treatments B and A were 91.3% and 94.5% respectively of tha t of treatment C. The results of these studies indicate that trovaflox acin has good oral bioavailability and that the ingestion of food is u nlikely to have a clinically significant effect on the bioavailability of trovafloxacin.