EXCRETION AND METABOLISM OF TROVAFLOXACIN IN HUMANS

The metabolism and excretion of trovafloxacin was investigated in four healthy male volunteers after a single oral administration of 200 mg of [C-14]trovafloxacin (118 mu Ci). Mean values of 23.1 and 63.3% of t he administered dose were recovered in the urine and feces, respective ly, after 240 hr. The C-max of total radioactivity and unchanged trova floxacin in serum was 3.2 mu g-equiv/ml and 2.9 mu g/ml, respectively, and peaked in 1.4 hr. The mean AUC(0-infinity) for radioactivity and trovafloxacin was 58.2 mu g-eq . hr/ml and 32.2 mu g . hr/ml, respecti vely. This implied that unchanged trovafloxacin constituted 55% of the circulating radioactivity. Urine and fecal samples were analyzed by L C/MS/MS for characterization of the metabolites, and the quantity of e ach metabolite in the matrices was assessed by means of a radioactivit y detector. The profile of radioactivity in urine showed three main me tabolites that were identified as the trovafloxacin glucuronide (M1), N-acetyltrovafloxacin glucuronide (M2), and N-acetyltrovafloxacin (M3) . The major fecal metabolites were M3 and the sulfate conjugate of tro vafloxacin (M4). Analysis of circulating metabolites from pooled serum extracts obtained at 1, 5, and 12 hr indicated that M1 was the major circulating metabolite (22% of circulating radioactivity), whereas M2 and M3 were detected in minor amounts. The results of the present stud y revealed that oxidative metabolism did not play a significant role i n the elimination of trovafloxacin, and phase II conjugation was the p rimary route of trovafloxacin clearance in humans.