Pharmacokinetics of [14C]FCE 22891, a penem antibiotic, following oral administration to healthy volunteers.
FCE 22891 is a prodrug of the penem antibiotic FCE 22101 and is suitable for oral administration. The pharmacokinetics of FCE 22891 were investigated in four healthy male volunteers following the oral administration of 500 mg of [14C]FCE 22891. Levels of radioactivity in plasma were always higher and persisted for longer than those of FCE 22101. The time to the maximum concentration of radioactivity in plasma generally coincided with that of FCE 22101. The respective values for the maximum concentrations of radioactivity in plasma were, on average, 8.57 +/- 2.95 micrograms equivalent/ml and 2.97 +/- 2.05 micrograms/ml. Over a 5-day period, mean urinary and fecal recovery of radioactivity accounted for 53.2 and 41.0% of the dose, respectively. The average amount of FCE 22101 excreted in urine and feces corresponded to 9.0 and 1.6% of the dose, respectively. The urinary recovery of the open-ring metabolite P1 and of its 5-S epimer P2 accounted for about 6.5 and 1.2% of the dose, respectively. Other chromatographic peaks corresponding to nonidentified compounds accounted for about 14.0% (polar metabolite fraction; peak P), 3.7% (less polar fraction; peak X), and 15.4% (least polar fraction) of the dose. Elimination of radioactivity and FCE 22101 in urine was rapid. Intersubject variability in the kinetics of total radioactivity in plasma was far less than that observed for FCE 22101. The results of the present study support suggestions that presystemic metabolism of FCE 22101 and/or transformation of the prodrug to compounds other than FCE 22101 are the main cause of intersubject variability in the kinetics of FCE 22101 produced in plasma following oral administration of its prodrug.
Efthymiopoulos
C
C
Farmitalia Carlo Erba, Milan, Italy.
Strolin Benedetti
M
M
Sassella
D
D
Boobis
A
A
Davies
D
D
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015780:Carbapenems / Q000493:pharmacokinetics; D005243:Feces / Q000737:chemistry; D006801:Humans; D007408:Intestinal Absorption; D007769:Lactams; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D007769:Lactams; D011355:Prodrugs; C041561:FCE 22891; C040033:ritipenem