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. 1992 Jan;36(1):217–219. doi: 10.1128/aac.36.1.217

Comparison of SCH 39304 and its isomers, RR 42427 and SS 42426, for treatment of murine cryptococcal and coccidioidal meningitis.

R Allendoerfer 1, R R Yates 1, A J Marquis 1, D Loebenberg 1, M G Rinaldi 1, J R Graybill 1
PMCID: PMC189266  PMID: 1590692

Abstract

SCH 39304 (304) and its isomers, SCH 42426 (426) and SCH 42427 (427), are new orally administered antifungal azole derivatives. In this study, we compared the efficacy of 304 with that of 426 and 427 in murine models of cryptococcal and coccidioidal meningitis. On day 18 postinfection with Cryptococcus neoformans, controls showed 80% mortality. The 50% protective doses calculated at this day were 0.56 mg of 304 per kg of body weight, 23.5 mg of 426 per kg, and 0.11 mg of 427 per kg. Controls with coccidioidal meningitis all succumbed, and treated mice at the same time point showed 50% protective doses of 10.8 mg/kg for 304, 200 mg/kg for 426, and 2.1 mg/kg for 427. We conclude that isomer 427 is five times as potent, whereas 426 is 1/50th as potent as 304 in these experimental mycoses.

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Selected References

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

  1. Bouza E., Dreyer J. S., Hewitt W. L., Meyer R. D. Coccidioidal meningitis. An analysis of thirty-one cases and review of the literature. Medicine (Baltimore) 1981 May;60(3):139–172. [PubMed] [Google Scholar]
  2. Clemons K. V., Hanson L. H., Perlman A. M., Stevens D. A. Efficacy of SCH39304 and fluconazole in a murine model of disseminated coccidioidomycosis. Antimicrob Agents Chemother. 1990 May;34(5):928–930. doi: 10.1128/aac.34.5.928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Defaveri J., Sun S. H., Graybill J. R. Treatment of murine coccidioidal meningitis with SCH39304. Antimicrob Agents Chemother. 1990 Apr;34(4):663–664. doi: 10.1128/aac.34.4.663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Drutz D. J. Amphotericin B in the treatment of coccidioidomycosis. Drugs. 1983 Oct;26(4):337–346. doi: 10.2165/00003495-198326040-00003. [DOI] [PubMed] [Google Scholar]
  5. Graybill J. R., Sun S. H., Ahrens J. Treatment of murine coccidioidal meningitis with fluconazole (UK 49,858). J Med Vet Mycol. 1986 Apr;24(2):113–119. doi: 10.1080/02681218680000171. [DOI] [PubMed] [Google Scholar]
  6. Harris S. C., Wallace J. E., Foulds G., Rinaldi M. G. Assay of fluconazole by megabore capillary gas-liquid chromatography with nitrogen-selective detection. Antimicrob Agents Chemother. 1989 May;33(5):714–716. doi: 10.1128/aac.33.5.714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. McIntyre K. A., Galgiani J. N. In vitro susceptibilities of yeasts to a new antifungal triazole, SCH 39304: effects of test conditions and relation to in vivo efficacy. Antimicrob Agents Chemother. 1989 Jul;33(7):1095–1100. doi: 10.1128/aac.33.7.1095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Perfect J. R., Wright K. A., Hobbs M. M., Durack D. T. Treatment of experimental cryptococcal meningitis and disseminated candidiasis with SCH39304. Antimicrob Agents Chemother. 1989 Oct;33(10):1735–1740. doi: 10.1128/aac.33.10.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Stamm A. M., Diasio R. B., Dismukes W. E., Shadomy S., Cloud G. A., Bowles C. A., Karam G. H., Espinel-Ingroff A. Toxicity of amphotericin B plus flucytosine in 194 patients with cryptococcal meningitis. Am J Med. 1987 Aug;83(2):236–242. doi: 10.1016/0002-9343(87)90691-7. [DOI] [PubMed] [Google Scholar]
  10. Tanio T., Ichise K., Nakajima T., Okuda T. In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent. Antimicrob Agents Chemother. 1990 Jun;34(6):980–984. doi: 10.1128/aac.34.6.980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Telzak E. E., Cote R. J., Gold J. W., Campbell S. W., Armstrong D. Extrapulmonary Pneumocystis carinii infections. Rev Infect Dis. 1990 May-Jun;12(3):380–386. doi: 10.1093/clinids/12.3.380. [DOI] [PubMed] [Google Scholar]
  12. Tucker R. M., Denning D. W., Dupont B., Stevens D. A. Itraconazole therapy for chronic coccidioidal meningitis. Ann Intern Med. 1990 Jan 15;112(2):108–112. doi: 10.7326/0003-4819-112-2-108. [DOI] [PubMed] [Google Scholar]
  13. Zuger A., Louie E., Holzman R. S., Simberkoff M. S., Rahal J. J. Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Diagnostic features and outcome of treatment. Ann Intern Med. 1986 Feb;104(2):234–240. doi: 10.7326/0003-4819-104-2-234. [DOI] [PubMed] [Google Scholar]

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