ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF CEFOTETAN (YM09330), A NEW BROAD SPECTRUM CEPHAMYCIN, IN EXPERIMENTAL ANIMALS

• Published in: CHEMOTHERAPY Vol. 30; no. Supplement1; pp. 106 - 118
• Main Authors: KOMIYA, MASAYUKI, KIKUCHI, YASUHIRO, TACHIBANA, AKIO, YANO, KUNIICHIRO
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 1982
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.30.Supplement1_106

Cefotetan (CTT, YM09330) was subcutaneously or intravenously administered to mice, rats, rabbits, dogs and monkeys in single doses of 20, 50 or 100 mg/kg, and the pharmacokinetic profiles of cefotetan were compared with those of cefmetazole and cefazolin. The plasma levels of cefotetan after a single dose of 20 mg/kg were highest in monkeys, followed by dogs, rabbits, rats and mice in that order, and the plasma half-lives of cefotetan were 75.6, 55.5, 30.5, 15.9 and 13.0 minutes, respectively. Those of cefotetan in mice, rats and rabbits were shorter than those of cefazolin and it was about the same as that of cefazolin in dogs. In comparison with cefmetazole, however, the plasma halflives of cefotetan were longer in all animal species tested. Cefotetan was rapidly distributed into various tissues of mice, rats and dogs. The concentrations in the tissues of the rat were proportional to doses and were highest in the kidney, followed by the plasma, liver, lung, heart and spleen in that order. The distribution patterns of cefotetan in mice and rats were similar to those of cefazolin. They were different from that of cefmetazole in the concentrations of the drugs in the liver. Urinary recoveries of cefotetan in mice, rats, dogs and monkeys over a 24-hour period were ranged from 50% to 67% of the administered dose and 74% of the dose was recovered in rabbit urine. Biliary recoveries were about 48% in rats, 5% in rabbits and 17% in dogs. Fecal recoveries of cefotetan of 38% of the dose for rats and 13% for dogs seemed to be comparable to the recoveries in bile of these animal species. By means of TLC-bioautography, no active metabolite of cefotetan was detected in the urine and bile of animals tested. However, an antibacterial active tautomer of cefotetan was observed in urine of all species. The extent of serum protein binding of cefotetan measured by centrifugal ultrafiltration method were 47% for mice, 30% for rabbits, 39% for dogs, 87% for monkeys and 91% for humans.