Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1986 Jun;29(6):1017–1024. doi: 10.1128/aac.29.6.1017

Disposition of carumonam (AMA-1080/Ro 17-2301), a new N-sulfonated monocyclic beta-lactam, in rats and dogs.

K Yoshida, M Mitani, I Naeshiro, H Torii, S Tanayama
PMCID: PMC180494  PMID: 3729358

Abstract

Rats and dogs were given a single 20-mg/kg dose of [14C]carumonam intramuscularly or intravenously. In rats, the level in plasma of [14C]carumonam administered intramuscularly peaked (29.1 micrograms/ml) 15 min after dosing and then declined with an apparent elimination half-life of 16.2 min. Intramuscular injection of [14C]carumonam to dogs gave a peak level (36.8 micrograms/ml) in plasma at 20 min and an apparent elimination half-life of 51.7 min. After administration of the intravenous dose, apparent elimination half-lives were 13.1 and 52.7 min in rats and dogs, respectively. In both animals, the radioactivity in plasma was made up largely (greater than 80%) of unchanged carumonam, which was protein bound to only a small extent. In rats given [14C]carumonam intramuscularly, radioactivity was distributed widely in tissues, with relatively high concentrations in the kidney and liver. The radioactivity concentration in the rat fetus was relatively low, as was that in milk. In both rats and dogs carumonam did not undergo extensive metabolism; the most prominent metabolite was AMA-1294, the compound resulting from beta-lactam ring hydrolysis. [14C]carumonam and metabolites were mostly eliminated from the bodies within 72 h in rats and 120 h in dogs. In both animals, a large amount of the dosed radioactivity was excreted in the urine largely as unchanged antibiotic. The remainder was eliminated in the feces via bile. AMA-1294 was eliminated from the bodies of rats and dogs at a considerably slower rate than was unchanged carumonam. In rats, [14C]carumonam was eliminated by both glomerular filtration (67%) and tubular secretion (33%); the renal elimination of [14C]AMA-1294 was only by glomerular filtration.

Full text

PDF
1017

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chamberlain J., Coombes J. D., Dell D., Fromson J. M., Ings R. J., Macdonald C. M., McEwen J. Metabolism of cefotaxime in animals and man. J Antimicrob Chemother. 1980 Sep;6 (Suppl A):69–78. doi: 10.1093/jac/6.suppl_a.69. [DOI] [PubMed] [Google Scholar]
  2. Cole M., Kenig M. D., Hewitt V. A. Metabolism of penicillins to penicilloic acids and 6-aminopenicillanic acid in man and its significance in assessing penicillin absorption. Antimicrob Agents Chemother. 1973 Apr;3(4):463–468. doi: 10.1128/aac.3.4.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Imada A., Kondo M., Okonogi K., Yukishige K., Kuno M. In vitro and in vivo antibacterial activities of carumonam (AMA-1080), a new N-sulfonated monocyclic beta-lactam antibiotic. Antimicrob Agents Chemother. 1985 May;27(5):821–827. doi: 10.1128/aac.27.5.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Kishimoto S., Sendai M., Hashiguchi S., Tomimoto M., Satoh Y., Matsuo T., Kondo M., Ochiai M. Synthesis of sulfazecin-type 2-azetidinones with a carbon substituent at the 4-position. J Antibiot (Tokyo) 1983 Oct;36(10):1421–1424. doi: 10.7164/antibiotics.36.1421. [DOI] [PubMed] [Google Scholar]
  5. Kobayashi T., Yoshida K., Mitani M., Torii H., Tanayama S. Metabolism of idebenone (CV-2619), a new cerebral metabolism improving agent: isolation and identification of metabolites in the rat and dog. J Pharmacobiodyn. 1985 Jun;8(6):448–456. doi: 10.1248/bpb1978.8.448. [DOI] [PubMed] [Google Scholar]
  6. Kozatani J., Okui M., Noda K., Ogino T., Noguchi H. Cefazolin, a new semisynthetic cephalosporin antibiotic. V. Distribution of cefazolin- 14 C in mice and rats after parenteral administration. Chem Pharm Bull (Tokyo) 1972 Jun;20(6):1105–1113. doi: 10.1248/cpb.20.1105. [DOI] [PubMed] [Google Scholar]
  7. Kripalani K. J., Singhvi S. M., Weinstein S. H., Everett D. W., Bathala M. S., Dean A. V., Ita C. E., Lawrence L., Meeker F. S., Jr, Shaw J. M. Disposition of [14C]aztreonam in rats, dogs, and monkeys. Antimicrob Agents Chemother. 1984 Aug;26(2):119–126. doi: 10.1128/aac.26.2.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. MALVIN R. L., WILDE W. S., SULLIVAN L. P. Localization of nephron transport by stop flow analysis. Am J Physiol. 1958 Jul;194(1):135–142. doi: 10.1152/ajplegacy.1958.194.1.135. [DOI] [PubMed] [Google Scholar]
  9. Matsuzaki M., Matsumoto H., Ochiai K., Tashiro Y., Hino M. [Absorption, distribution and excretion of 14C-cefatrizine (14C-S-640 P) in rat (author's transl)]. Jpn J Antibiot. 1976 Apr;29(4):391–402. [PubMed] [Google Scholar]
  10. McNulty C. A., Garden G. M., Ashby J., Wise R. Pharmacokinetics and tissue penetration of carumonam, a new synthetic monobactam. Antimicrob Agents Chemother. 1985 Sep;28(3):425–427. doi: 10.1128/aac.28.3.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nakai Y., Kanai Y., Fugono T., Tanayama S. Metabolic fate of cephacetrile after parenteral administration in rats and rabbits. J Antibiot (Tokyo) 1976 Jan;29(1):81–90. doi: 10.7164/antibiotics.29.81. [DOI] [PubMed] [Google Scholar]
  12. Nightingale C. H., Greene D. S., Quintiliani R. Pharmacokinetics and clinical use of cephalosporin antibiotics. J Pharm Sci. 1975 Dec;64(12):1899–1926. doi: 10.1002/jps.2600641202. [DOI] [PubMed] [Google Scholar]
  13. Nishida M., Murakawa T., Kamimura T., Okada N., Sakamoto H., Fukada S., Nakamoto S., Yokota Y., Miki K. In vitro and in vivo evaluation of ceftezole, a new cephalosporin derivative. Antimicrob Agents Chemother. 1976 Jul;10(1):1–13. doi: 10.1128/aac.10.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Reeves D. S., White L. O., Holt H. A., Bahari D., Bywater M. J., Bax R. P. Human metabolism of cefotaxime. J Antimicrob Chemother. 1980 Sep;6 (Suppl A):93–101. doi: 10.1093/jac/6.suppl_a.93. [DOI] [PubMed] [Google Scholar]
  15. Singhvi S. M., Ita C. E., Shaw J. M., Keim G. R., Migdalof B. H. Distribution of aztreonam into fetuses and milk of rats. Antimicrob Agents Chemother. 1984 Aug;26(2):132–135. doi: 10.1128/aac.26.2.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Swabb E. A., Singhvi S. M., Leitz M. A., Frantz M., Sugerman A. Metabolism and pharmacokinetics of aztreonam in healthy subjects. Antimicrob Agents Chemother. 1983 Sep;24(3):394–400. doi: 10.1128/aac.24.3.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tanayama S., Momose S., Kanai Y., Shirakawa Y. Metabolism of 8-chloro-6-phenyl-4H-s-triazolo(4,3-a)-(1,4)benzodiazepine (D-40TA), a new central depressant. IV. Placental transfer and excretion in milk in rats. Xenobiotica. 1974 Apr;4(4):219–227. doi: 10.3109/00498257409062540. [DOI] [PubMed] [Google Scholar]
  18. Tanayama S., Shirakawa Y., Kanai Y., Suzuoki Z. Metabolism of 8-chloro-6-phenyl-4H-s-triazolo(4,3-a)(1,4)-benzodiazepine (D-40TA), a new central depressant. I. Absorption, distribution and excretion in rats. Xenobiotica. 1974 Jan;4(1):33–47. doi: 10.3109/00498257409052088. [DOI] [PubMed] [Google Scholar]
  19. Tanayama S., Yoshida K., Adachi K., Kondo T. Metabolic fate of SCE-1365, a new broad-spectrum cephalosporin, after parenteral administration to rats and dogs. Antimicrob Agents Chemother. 1980 Oct;18(4):511–518. doi: 10.1128/aac.18.4.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tanayama S., Yoshida K., Kanai Y. Metabolic fate of SCE-129, a new antipseudomonal cephalosporin, after parenteral administration in rats and dogs. Antimicrob Agents Chemother. 1978 Jul;14(1):137–143. doi: 10.1128/aac.14.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. WILLIAMSON H. E., SKULAN T. W., SHIDEMAN F. E. Effects of adrenalectomy and desoxycorticosterone on stop-flow patterns of sodium and potassium in the rat. J Pharmacol Exp Ther. 1961 Jan;131:49–55. [PubMed] [Google Scholar]
  22. Weidekamm E., Stoeckel K., Egger H. J., Ziegler W. H. Single-dose pharmacokinetics of Ro 17-2301 (AMA-1080), a monocyclic beta-lactam, in humans. Antimicrob Agents Chemother. 1984 Dec;26(6):898–902. doi: 10.1128/aac.26.6.898. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES