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. 1987 Nov;31(11):1756–1760. doi: 10.1128/aac.31.11.1756

Comparative in vitro and in vivo evaluation of N-D-ornithyl amphotericin B methyl ester, amphotericin B methyl ester, and amphotericin B.

R M Parmegiani 1, D Loebenberg 1, B Antonacci 1, T Yarosh-Tomaine 1, R Scupp 1, J J Wright 1, P J Chiu 1, G H Miller 1
PMCID: PMC175034  PMID: 3324961

Abstract

N-D-Ornithyl amphotericin B methyl ester (O-AME), a semisynthetic derivative of amphotericin B methyl ester (AME), was compared with amphotericin B (AMB) and AME. In vitro, O-AME was more active than the other two against Candida spp. and other fungi and was only slightly affected by inoculum size, addition of serum, or changes in pH. In vivo, the dose of O-AME required to produce a 10,000-fold reduction of Candida albicans in a mouse kidney infection was similar to that of AMB and 1/10 that of AME. After intravenous treatment of infected mice and rats and subcutaneous treatment of mice, average 50% protective doses for O-AME and AMB were similar. Acute intravenous 50% lethal doses in mice indicated that O-AME was one-ninth as toxic as AMB but twice as toxic as AME. Acute renal function tests in rats indicated that Sch 28191 was less than 1/10 as toxic as AMB and slightly more toxic than AME. On this basis, the calculated advantage relative to AMB (with AMB equal to 1) was 8 for O-AME and 1.5 for AME.

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Selected References

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

  1. Bonner D. P., Tewari R. P., Solotorovsky M., Mechlinski W., Schaffner C. P. Comparative chemotherapeutic activity of amphotericin B and amphotericine B methy ester. Antimicrob Agents Chemother. 1975 Jun;7(6):724–729. doi: 10.1128/aac.7.6.724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chiu P. J., Miller G. H., Brown A. D., Long J. F., Waitz J. A. Renal pharmacology of netilmicin. Antimicrob Agents Chemother. 1977 May;11(5):821–825. doi: 10.1128/aac.11.5.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ellis W. G., Sobel R. A., Nielsen S. L. Leukoencephalopathy in patients treated with amphotericin B methyl ester. J Infect Dis. 1982 Aug;146(2):125–137. doi: 10.1093/infdis/146.2.125. [DOI] [PubMed] [Google Scholar]
  4. Gadebusch H. H., Pansy F., Klepner C., Schwind R. Amphotericin B and amphotericin B methyl ester ascorbate. I. Chemotherapeutic activity against Candida albicans, Cryptococcus neoformans, and Blastomyces dermatitidis in mice. J Infect Dis. 1976 Nov;134(5):423–427. doi: 10.1093/infdis/134.5.423. [DOI] [PubMed] [Google Scholar]
  5. Galgiani J. N., VanWyck D. B. Ornithyl amphotericin methyl ester treatment of experimental candidiasis in rats. Antimicrob Agents Chemother. 1984 Jul;26(1):108–109. doi: 10.1128/aac.26.1.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Graybill J. R., Kaster S. R. Experimental murine aspergillosis. Comparison of amphotericin B and a new polyene antifungal drug, SCH 28191. Am Rev Respir Dis. 1984 Feb;129(2):292–295. [PubMed] [Google Scholar]
  7. Keim G. R., Jr, Poutsiaka J. W., Kirpan J., Keysser C. H. Amphotericin B methyl ester hydrochloride and amphotericin B: comparative acute toxicity. Science. 1973 Feb 9;179(4073):584–585. doi: 10.1126/science.179.4073.584. [DOI] [PubMed] [Google Scholar]
  8. Keim G. R., Sibley P. L., Yoon Y. H., Kulesza J. S., Zaidi I. H., Miller M. M., Poutsiaka J. W. Comparative toxicological studies of amphotericin B methyl ester and amphotericin B in mice, rats, and dogs. Antimicrob Agents Chemother. 1976 Oct;10(4):687–690. doi: 10.1128/aac.10.4.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kim H., Loebenberg D., Marco A., Symchowicz S., Lin C. Comparative pharmacokinetics of Sch 28191 and amphotericin B in mice, rats, dogs, and cynomolgus monkeys. Antimicrob Agents Chemother. 1984 Oct;26(4):446–449. doi: 10.1128/aac.26.4.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kobayashi G. S., Little J. R., Medoff G. In vitro and in vivo comparisons of amphotericin B and N-D-ornithyl amphotericin B methyl ester. Antimicrob Agents Chemother. 1985 Mar;27(3):302–305. doi: 10.1128/aac.27.3.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lawrence R. M., Hoeprich P. D. Comparison of amphotericin B and amphotericin B methyl ester: efficacy in murine coccidioidomycosis and toxicity. J Infect Dis. 1976 Feb;133(2):168–174. doi: 10.1093/infdis/133.2.168. [DOI] [PubMed] [Google Scholar]
  12. Lefler E., Brummer E., Perlman A. M., Stevens D. A. Activities of the modified polyene N-D-ornithyl amphotericin methyl ester and the azoles ICI 153066, Bay n 7133, and Bay l 9139 compared with those of amphotericin B and ketoconazole in the therapy of experimental blastomycosis. Antimicrob Agents Chemother. 1985 Mar;27(3):363–366. doi: 10.1128/aac.27.3.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Massa T., Sinha D. P., Frantz J. D., Filipek M. E., Weglein R. C., Steinberg S. A., McGrath J. T., Murphy B. F., Szot R. J., Black H. E. Subchronic toxicity studies of N-D-ornithyl amphotericin B methyl ester in dogs and rats. Fundam Appl Toxicol. 1985 Aug;5(4):737–753. doi: 10.1016/0272-0590(85)90198-8. [DOI] [PubMed] [Google Scholar]
  14. Oblack D. L., Hewitt W. L., Martin W. J. Comparative in vitro susceptibility of yeasts to amphotericin B and three methyl ester derivatives. Antimicrob Agents Chemother. 1981 Jan;19(1):106–109. doi: 10.1128/aac.19.1.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Perfect J. R., Durack D. T. Comparison of amphotericin B and N-D-ornithyl amphotericin B methyl ester in experimental cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis. Antimicrob Agents Chemother. 1985 Dec;28(6):751–755. doi: 10.1128/aac.28.6.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Schaffner C. P., Mechlinski W. Polyene macrolide derivatives. II. Physical-chemical properties of polyene macrolide esters and their water soluble salts. J Antibiot (Tokyo) 1972 Apr;25(4):259–260. [PubMed] [Google Scholar]
  17. Wright J. J., Albarella J. A., Krepski L. R., Loebenberg D. N-aminoacyl derivatives of polyene macrolide antibiotics and their esters. J Antibiot (Tokyo) 1982 Jul;35(7):911–914. doi: 10.7164/antibiotics.35.911. [DOI] [PubMed] [Google Scholar]

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