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Toxicity of amphotericins on chronic administration to mongrel dogs
Diagnostic Microbiology and Infectious Disease
|January 1, 1985
Abstract:
Conditioned mongrel dogs were given 30 i.v. injections of either AMB (amphotericin B, 0.75 mg/kg body weight), AME (amphotericin B methyl ester, 10 mg/kg body weight), or 5% glucose solution without antimicrobic. Severe loss of body weight and nephrotoxicity occurred with AMB; hepatic dysfunction resulted with AME; astrogliosis and pallor of the myelin were found in dogs given AME and 5% glucose solution.
Insights
Amphotericin B (AMB) caused severe weight loss and kidney damage in dogs. Amphotericin B methyl ester (AME) led to liver issues and neurological changes, indicating significant toxicity for both antifungal drugs.
Area of Science:
- Pharmacology
- Toxicology
- Veterinary Medicine
Background:
- Antifungal medications are crucial for treating systemic fungal infections.
- Amphotericin B (AMB) is a widely used antifungal agent but is associated with significant toxicity.
- Amphotericin B methyl ester (AME) was developed as a potentially less toxic alternative.
Purpose of the Study:
- To compare the toxicity profiles of Amphotericin B (AMB) and Amphotericin B methyl ester (AME) in a canine model.
- To evaluate the specific organ toxicities associated with intravenous administration of AMB and AME.
Main Methods:
- Mongrel dogs received 30 intravenous injections of either AMB (0.75 mg/kg), AME (10 mg/kg), or a 5% glucose control solution.
- Clinical signs, body weight changes, and evidence of organ damage were monitored.
- Histopathological examination focused on kidney, liver, and central nervous system tissues.
Main Results:
- Amphotericin B (AMB) treatment resulted in severe body weight loss and significant nephrotoxicity.
- Amphotericin B methyl ester (AME) administration led to hepatic dysfunction.
- Both AME and the 5% glucose control solution were associated with astrogliosis and myelin pallor in the central nervous system.
Conclusions:
- Intravenous Amphotericin B (AMB) exhibits significant nephrotoxic and catabolic effects in dogs.
- Amphotericin B methyl ester (AME) demonstrates hepatotoxicity and potential neurotoxicity in the canine model.
- Both AMB and AME present distinct toxicity profiles, necessitating careful clinical consideration.