The disposition and urinary metabolism of 14C-labelled FCE 22891, a pro-drug of FCE 22101, in animals.
[2-14C]FCE 22891 was given orally and intravenously to the rat, orally to the dog and monkey. Radioactivity was eliminated by both the renal and faecal route after oral administration, but mainly in the urine after the iv route in the rat. Radioactivity as expired 14CO2 was detected in the rat and accounted for less than 1% of the dose after iv and 3.2% after oral dosage within 72 h. After oral FCE 22891 labelled by 14C in the acetoxymethyl moiety, radioactivity recovered as expired 14CO2 accounted for over 55% of the dose at 72 h in the rat. No FCE 22891 was detected in plasma, whereas consistent amounts of FCE 22101 were detected. The metabolism was studied by radio-HPLC in the urine of the animals treated with [2-14C]FCE 22891. No unchanged drug was detected at any time interval. FCE 22101 was the main urinary metabolite with the exception of the dog and accounted for about one-half of the radioactivity excreted in 0-24 h urine. Significant amounts of metabolite P1, an open beta-lactam ring derivative obtained by action of dehydropeptidase, were found in the urine of rat and monkey but not in the dog. The remaining urinary radioactivity was due to other metabolites, named P, X and LP, which might originate from P1, as stability of P1 is pH-dependent.
Battaglia
R
R
Farmitalia Carlo Erba, Research and Development, Milan, Italy.
Benedetti
M S
MS
Frigerio
E
E
Vicario
G
G
Roncucci
R
R
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine*; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005243:Feces; D005260:Female; D006868:Hydrolysis; D007275:Injections, Intravenous; D007700:Kinetics; D007769:Lactams; D008252:Macaca fascicularis; D008297:Male; D011355:Prodrugs / Q000032:analysis* / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains
D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D007769:Lactams; D011355:Prodrugs; C041561:FCE 22891