In Vivo Efficacy of SM-8668 (Sch 39304), a New Oral Triazole Antifungal Agent

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1990 Jun 1

PMID 2203310

Citations 5

Authors

T Tanio

K Ichise

T Nakajima

T Okuda

Affiliations

Soon will be listed here.

Abstract

SM-8668 (Sch 39304) is a new oral antifungal agent which we evaluated in comparison with fluconazole in various fungal infection models. The prophylactic effect of SM-8668 was excellent against systemic candidiasis, aspergillosis, and cryptococcosis in mice. The 50% effective dose for SM-8668 was assessed at 10 days after infection and was 0.18, 3.7, and 5.9 mg/kg (body weight), respectively, for the above-mentioned fungal diseases. Fluconazole was about four times less effective than SM-8668 against systemic candidiasis and was only slightly effective at doses of 80 and 25 mg/kg against systemic aspergilosis and cryptococcosis, respectively. SM-8668 was also about four to eight times more active than fluconazole against vaginal candidiasis in rats and against dermatophytic infection in guinea pigs. In addition, topical SM-8668 was as effective as topical miconazole or tioconazole against skin mycosis in guinea pigs. After oral administration, SM-8668 showed a maximum concentration in serum similar to that of fluconazole in both mice and rats, but the elimination half-life and area under the serum concentration-time curve for SM-8668 were twice those for fluconazole.

Citing Articles

In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum.

Hata K, Kimura J, Miki H, Toyosawa T, Nakamura T, Katsu K Antimicrob Agents Chemother. 1996; 40(10):2237-42.

PMID: 8891121 PMC: 163510. DOI: 10.1128/AAC.40.10.2237.

Pharmacokinetics of the triazole antifungal agent genaconazole in healthy men after oral and intravenous administration.

Mojaverian P, Radwanski E, Affrime M, CAYEN M, Lin C Antimicrob Agents Chemother. 1994; 38(12):2758-62.

PMID: 7695258 PMC: 188281. DOI: 10.1128/AAC.38.12.2758.

In vitro and in vivo activities of SCH 42427, the active enantiomer of the antifungal agent SCH 39304.

Loebenberg D, Cacciapuoti A, PARMEGIANI R, Moss Jr E, Menzel Jr F, Antonacci B Antimicrob Agents Chemother. 1992; 36(2):498-501.

PMID: 1605621 PMC: 188469. DOI: 10.1128/AAC.36.2.498.

Comparison of SCH 39304, fluconazole, and ketoconazole for treatment of systemic infections in mice.

Cacciapuoti A, Loebenberg D, PARMEGIANI R, Antonacci B, Norris C, Moss Jr E Antimicrob Agents Chemother. 1992; 36(1):64-7.

PMID: 1590702 PMC: 189227. DOI: 10.1128/AAC.36.1.64.

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

Allendoerfer R, Yates R, Marquis A, Loebenberg D, Rinaldi M, Graybill J Antimicrob Agents Chemother. 1992; 36(1):217-9.

PMID: 1590692 PMC: 189266. DOI: 10.1128/AAC.36.1.217.

References

Yozwiak M, Galgiani J . Itraconazole treatment of experimental systemic candidiasis in male rats. J Med Vet Mycol. 1987; 25(2):125-6. DOI: 10.1080/02681218780000171. View

Fierer J, Kirkland T, Finley F . Comparison of fluconazole and SDZ89-485 for therapy of experimental murine coccidioidomycosis. Antimicrob Agents Chemother. 1990; 34(1):13-6. PMC: 171511. DOI: 10.1128/AAC.34.1.13. View

Van Cutsem J, Van Gerven F, Janssen P . Activity of orally, topically, and parenterally administered itraconazole in the treatment of superficial and deep mycoses: animal models. Rev Infect Dis. 1987; 9 Suppl 1:S15-32. DOI: 10.1093/clinids/9.supplement_1.s15. View

Ichise K, Tanio T, Saji I, Okuda T . Activity of SM-4470, a new imidazole derivative, against experimental fungal infections. Antimicrob Agents Chemother. 1986; 30(3):366-9. PMC: 180561. DOI: 10.1128/AAC.30.3.366. View

HUMPHREY M, Jevons S, Tarbit M . Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother. 1985; 28(5):648-53. PMC: 176350. DOI: 10.1128/AAC.28.5.648. View

Troke P, Andrews R, BRAMMER K, Marriott M, Richardson K . Efficacy of UK-49,858 (fluconazole) against Candida albicans experimental infections in mice. Antimicrob Agents Chemother. 1985; 28(6):815-8. PMC: 180335. DOI: 10.1128/AAC.28.6.815. View

Van Cutsem J, Van Gerven F, Van de Ven M, Borgers M, Janssen P . Itraconazole, a new triazole that is orally active in aspergillosis. Antimicrob Agents Chemother. 1984; 26(4):527-34. PMC: 179958. DOI: 10.1128/AAC.26.4.527. View

PLEMPEL M . Antimycotic activity of BAY N 7133 in animal experiments. J Antimicrob Chemother. 1984; 13(5):447-63. DOI: 10.1093/jac/13.5.447. View

Troke P, Andrews R, Marriott M, Richardson K . Efficacy of fluconazole (UK-49,858) against experimental aspergillosis and cryptococcosis in mice. J Antimicrob Chemother. 1987; 19(5):663-70. DOI: 10.1093/jac/19.5.663. View

10.

Vant Wout J, Mattie H, Van Furth R . A prospective study of the efficacy of fluconazole (UK-49,858) against deep-seated fungal infections. J Antimicrob Chemother. 1988; 21(5):665-72. DOI: 10.1093/jac/21.5.665. View

11.

Stern J, Hartman B, Sharkey P, Rowland V, Squires K, Murray H . Oral fluconazole therapy for patients with acquired immunodeficiency syndrome and cryptococcosis: experience with 22 patients. Am J Med. 1988; 85(4):477-80. DOI: 10.1016/s0002-9343(88)80081-0. View

12.

Sugar A, Saunders C . Oral fluconazole as suppressive therapy of disseminated cryptococcosis in patients with acquired immunodeficiency syndrome. Am J Med. 1988; 85(4):481-9. DOI: 10.1016/s0002-9343(88)80082-2. View

13.

Hardin T, Graybill J, Fetchick R, Woestenborghs R, Rinaldi M, Kuhn J . Pharmacokinetics of itraconazole following oral administration to normal volunteers. Antimicrob Agents Chemother. 1988; 32(9):1310-3. PMC: 175857. DOI: 10.1128/AAC.32.9.1310. View

14.

De Beule K, De Doncker P, Cauwenbergh G, Koster M, Legendre R, Blatchford N . The treatment of aspergillosis and aspergilloma with itraconazole, clinical results of an open international study (1982-1987). Mycoses. 1988; 31(9):476-85. DOI: 10.1111/j.1439-0507.1988.tb03653.x. View

15.

Ryley J, McGregor S, Wilson R . Activity of ICI 195,739--a novel, orally active bistriazole--in rodent models of fungal and protozoal infections. Ann N Y Acad Sci. 1988; 544:310-28. DOI: 10.1111/j.1749-6632.1988.tb40416.x. View

16.

Viviani M, Tortorano A, Langer M, Almaviva M, Negri C, Cristina S . Experience with itraconazole in cryptococcosis and aspergillosis. J Infect. 1989; 18(2):151-65. DOI: 10.1016/s0163-4453(89)91178-x. View

17.

Denning D, TUCKER R, Hanson L, Stevens D . Treatment of invasive aspergillosis with itraconazole. Am J Med. 1989; 86(6 Pt 2):791-800. DOI: 10.1016/0002-9343(89)90475-0. View

18.

McIntyre K, Galgiani J . 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; 33(7):1095-100. PMC: 176068. DOI: 10.1128/AAC.33.7.1095. View

19.

Restrepo B, Ahrens J, Graybill J . Efficacy of SCH39304 in murine cryptococcosis. Antimicrob Agents Chemother. 1989; 33(8):1242-6. PMC: 172633. DOI: 10.1128/AAC.33.8.1242. View

20.

Denning D, TUCKER R, Hanson L, Hamilton J, Stevens D . Itraconazole therapy for cryptococcal meningitis and cryptococcosis. Arch Intern Med. 1989; 149(10):2301-8. View