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Titolo:
Comparison of a new triazole antifungal agent, Schering 56592, with itraconazole and amphotericin B for treatment of histoplasmosis in immunocompetent mice
Autore:
Connolly, P; Wheat, J; Schnizlein-Bick, C; Durkin, M; Kohler, S; Smedema, M; Goldberg, J; Brizendine, E; Loebenberg, D;
Indirizzi:
Histoplasmosis Reference Lab, Indianapolis, IN 46202 USA Histoplasmosis Reference Lab Indianapolis IN USA 46202 olis, IN 46202 USA Indiana Univ, Sch Med, Dept Vet Affairs Hosp, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 s Hosp, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 pt Med, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 Pathol, Indianapolis, IN 46202 USA Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA Schering Plough Corp Kenilworth NJ USA 07033 st, Kenilworth, NJ 07033 USA
Titolo Testata:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
fascicolo: 2, volume: 43, anno: 1999,
pagine: 322 - 328
SICI:
0066-4804(199902)43:2<322:COANTA>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CAPSULATUM ANTIGEN; MURINE MODEL; IN-VITRO; FLUCONAZOLE; COCCIDIOIDOMYCOSIS; BLASTOMYCOSIS; SCH-56592; INVITRO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Wheat, J Histoplasmosis2Reference Lab, 1001 W 10th St,OPW 430, Indianapolis, IN 4620 Histoplasmosis Reference Lab 1001 W 10th St,OPW 430 IndianapolisIN USA 46202
Citazione:
P. Connolly et al., "Comparison of a new triazole antifungal agent, Schering 56592, with itraconazole and amphotericin B for treatment of histoplasmosis in immunocompetent mice", ANTIM AG CH, 43(2), 1999, pp. 322-328

Abstract

A murine model of intratracheally induced histoplasmosis was used to evaluate a new triazole antifungal agent, Schering (SCH) 56592, for treatment ofhistoplasmosis, MICs were determined for SCH 56592, amphotericin B, and itraconazole by testing yeast-phase isolates from 20 patients by a macrobrothdilution method. The MICs at which 90% of the isolates are inhibited were for 0.019 mu g/ml for SCH 56592, 0.5 mu g/ml for amphotericin B, and less than or equal to 0.019 mu g/ml for itraconazole. Survival studies were done on groups of 10 B6C3F(1) mice with a lethal inoculum of 10(5), All mice receiving 5, 1, or 0.25 mg of SCH 56592 per kg of body weight per day, 2.5 mg of amphotericin B per kg every other day (qod), or 75 mg of itraconazole per kg per day survived to day 29, Only 44% of mice receiving 5 mg of itraconazole/kg/day survived to day 29, Fungal burden studies done in similar groups of mice with a sublethal inoculum of 10(4) showed a reduction in CFUs and Histoplasma antigen levels in lung and spleen tissue in animals treated with 2 mg of amphotericin B/kg qod, 1 mg of SCH 56592/kg/day, and 75 mg of itraconazole/kg/day, but not in those treated with lower doses of the study drugs (0.2 mg of amphotericin B/kg god, 0.1 mg of SCH 56592/kg/day, or 10 mg of itraconazole/kg/day), Serum drug concentrations were measured 3 and 24h after the last dose in mice (groups of five to seven mice), each treatedfor 7 days with SCH 56592 (10 and 1 mg/kg/day) and itraconazole (75 and 10mg/kg/day). Mean levels measured by bioassay were as follows: SCH 56592, 10 mg/kg/day (2.15 mu g/ml at 3 h and 0.35 mu g/ml at 24 h); SCH 56592, 1 mg/kg/day (0.54 mu g/ml at 3 h and none detected at 24 h); itraconazole, 75 mg/kg/day (22.53 mu g/ml at 3 h and none detected at 24 h); itraconazole, 10mg/kg/day (1.33 mu g/ml at 3 h and none detected at 24 h), Confirmatory results were obtained by high-pressure liquid chromatography assay. These studies show SCH 56592 to be a promising candidate for studies of treatment ofhistoplasmosis in humans.

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Documento generato il 30/09/20 alle ore 08:07:20