Efficacy of the triazole SCH 56592 against Leishmania amazonensis and Leishmania donovani in experimental murine cutaneous and visceral leishmaniases

Hail M. Al-Abdely, John R. Graybill, David Loebenberg, Peter Melby

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Abstract

Current therapy for leishmaniasis is unsatisfactory. Efficacious and safe oral therapy would be ideal. We examined the efficacy of SCH 56592, an investigational triazole antifungal agent, against cutaneous infection with Leishmania amazonensis and visceral infection with Leishmania donovani in BALB/c mice. Mice were infected in the ear pinna and tail with L. amazonensis promastigotes and were treated with oral SCH 56592 or intraperitoneal amphotericin B for 21 days. At doses of 60 and 30 mg/kg/day, SCH 56592 was highly efficacious in treating cutaneous disease, and at a dose of 60 mg/kg/day, it was superior to amphotericin B at a dose of 1 mg/kg/day. The means of tail lesion sizes were 0.32 ± 0.12, 0.11 ± 0.06, 0.17 ± 0.07, and 0.19 ± 0.08 mm for controls, SCH 56592 at 60 and 30 mg/kg/day, and amphotericin B recipients, respectively (P = 0.0003, 0.005, and 0.01, respectively). Parasite burden in draining lymph nodes confirmed these efficacy findings. In visceral leishmaniasis due to L. donovani infection, mice treated with SCH 56592 showed a 0.5- to 1-log-unit reduction in parasite burdens in the liver and the spleen compared to untreated mice. Amphotericin B at 1 mg/kg/day was superior to SCH 56592 in the treatment of visceral infection, with a 2-log-unit reduction in parasite burdens in both the liver and spleen. These studies indicate very good activity of SCH 56592 against cutaneous leishmaniasis due to L. amazonensis infection and, to a lesser degree, against visceral leishmaniasis due to L. donovani infection in susceptible BALB/c mice.

Original languageEnglish (US)
Pages (from-to)2910-2914
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume43
Issue number12
StatePublished - 1999
Externally publishedYes

Fingerprint

Leishmania donovani
Triazoles
Skin
Amphotericin B
Infection
Parasites
Visceral Leishmaniasis
Tail
Ear Auricle
Spleen
Cutaneous Leishmaniasis
Leishmaniasis
Antifungal Agents
Leishmania
Liver
posaconazole
Skin Diseases
Lymph Nodes
Therapeutics

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Efficacy of the triazole SCH 56592 against Leishmania amazonensis and Leishmania donovani in experimental murine cutaneous and visceral leishmaniases. / Al-Abdely, Hail M.; Graybill, John R.; Loebenberg, David; Melby, Peter.

In: Antimicrobial Agents and Chemotherapy, Vol. 43, No. 12, 1999, p. 2910-2914.

Research output: Contribution to journalArticle

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abstract = "Current therapy for leishmaniasis is unsatisfactory. Efficacious and safe oral therapy would be ideal. We examined the efficacy of SCH 56592, an investigational triazole antifungal agent, against cutaneous infection with Leishmania amazonensis and visceral infection with Leishmania donovani in BALB/c mice. Mice were infected in the ear pinna and tail with L. amazonensis promastigotes and were treated with oral SCH 56592 or intraperitoneal amphotericin B for 21 days. At doses of 60 and 30 mg/kg/day, SCH 56592 was highly efficacious in treating cutaneous disease, and at a dose of 60 mg/kg/day, it was superior to amphotericin B at a dose of 1 mg/kg/day. The means of tail lesion sizes were 0.32 ± 0.12, 0.11 ± 0.06, 0.17 ± 0.07, and 0.19 ± 0.08 mm for controls, SCH 56592 at 60 and 30 mg/kg/day, and amphotericin B recipients, respectively (P = 0.0003, 0.005, and 0.01, respectively). Parasite burden in draining lymph nodes confirmed these efficacy findings. In visceral leishmaniasis due to L. donovani infection, mice treated with SCH 56592 showed a 0.5- to 1-log-unit reduction in parasite burdens in the liver and the spleen compared to untreated mice. Amphotericin B at 1 mg/kg/day was superior to SCH 56592 in the treatment of visceral infection, with a 2-log-unit reduction in parasite burdens in both the liver and spleen. These studies indicate very good activity of SCH 56592 against cutaneous leishmaniasis due to L. amazonensis infection and, to a lesser degree, against visceral leishmaniasis due to L. donovani infection in susceptible BALB/c mice.",
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