ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF CEFUROXIME AXETIL (CXM-AX) IN RATS AND DOGS

• Published in: CHEMOTHERAPY Vol. 34; no. Supplement5; pp. 343 - 353
• Main Authors: TAKEDA, KENZO, TSUJI, HIKOJI, FUKUDA, ICHIRO, NAGAKI, TAMEICHIRO, MORITA, TAKESHI, WATANABE, YOSHIE, TOSHIMITSU, YOSHINOBU, KINAMI, JUNJI, MANBO, KUNIHISA, OKIYAMA, MASAHIKO, OKUMURA, KAZUO
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Society of Chemotherapy 1986
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.34.Supplement5_343

Absorption, distribition, metabolism and excretion of cefuroxime (CXM) were investigated in rats and dogs after single oral administration of 20mg/kg of cefuroxime axetil (CXM-AX, SN 407), and the following results were obtained. 1. After an oral dose of CXM-AX, the peak serum or plasma levels of CXM were 5.52μg/ml at 30 mins in rats and 10.09μg/ml at 60 mins in dogs. The serum and plasma half-lives were 70.2 and 73.8 mins, respectively. 2. The peak serum level of CXM in rats was, when compared with other drugs, as high as those of CEX and CCL, but lower than that of CFT. The peak plasma level of CXM was about a half of that of CEX in dogs. 3. The tissue levels of CXM in rats were the highest in kidney, and the second highest, in liver. The CXM levels in lung, heart and spleen were low. 4. The 0-24 hr urinary excretion rate was 30.3% in rats and 29.4% in dogs, and most of the urinary excretion took place within 6 hours. The 0-24 hr biliary excretion in rats was 1.60%. 5. After CXM-AX (20mg/kg/day) was given to rats by p. o. for 21 consecutive days, the CXM levels in serum and organs, and urinary excretion rate were similar to those after a single dose, and no drug accumulation was observed. 6. After CXM-AX was given to male and female rats, the peak serum level, serum half-life, AUC and urinary excretion rate in male rats were similar to those in female rats, with no difference between sexes. 7. After CXM-AX was given to rats in the fasting and non-fasting groups, the peak serum level, serum half-life, AUC and urinary excretion rate were comparable in these two groups, and no influence of feeding on pharmacokinetics was observed. 8. Active metabolite of CXM-AX was sought by bioautography. As a results, only CXM was detected in serum, plasma or urine. 9. The in vitro serum protein binding rates of CXM in mice, rats, rabbits, dogs and humans were 17 1, 37.1, 42.9, 19.6 and 35.0%, respectively. The in vivo serum protein binding rates, determined with serum of rats given CXM-AX, ranged 31.9-40.4% which was consistent with the in vitro study result on rats.