Assuntos
Antagonistas Adrenérgicos beta/metabolismo , Nefropatias/metabolismo , Propanolaminas/metabolismo , Urânio/farmacologia , Nitrato de Uranil/farmacologia , Animais , Biotransformação , Cães , Taxa de Filtração Glomerular/efeitos dos fármacos , Nefropatias/induzido quimicamente , Cinética , MasculinoRESUMO
In acute and subacute toxicological studies, amphotericin B methyl ester was shown to be much less toxic than the parent antibiotic. As a single intravenous dose in mice, the methyl ester was approximately 20 times less toxic than amphotericin B. Also, the acute toxicity of the methyl ester in mice was not enhanced by the presence of chemically induced hepatic or renal damage or by the concurrent administration of amphotericin B or flucytosine. In a 1-month intraperitoneal study in rats, the methyl ester was about one-fourth as nephrotoxic as amphotericin B. In a 1-month intravenous study in dogs, the methyl ester was about one-eighth as nephrotoxic and one-fourth to one-half as hepatotoxic as the parent compound. In addition, the methyl ester, unlike amphotericin B, produced minimal renal effects, which did not increase in severity with increasing dosage. Based on the results of these studies, it is concluded that amphotericin B methyl ester has the potential for an improved therapeutic ratio in the treatment of systemic mycoses.
Assuntos
Anfotericina B/toxicidade , Anfotericina B/administração & dosagem , Anfotericina B/análogos & derivados , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cães , Feminino , Injeções Intraperitoneais , Injeções Intravenosas , Dose Letal Mediana , Masculino , Camundongos , Ratos , Especificidade da Espécie , Fatores de TempoRESUMO
In single-dose parenteral studies with mice and dogs, the methyl ester hydrochloride of amphotericin B proved to be significantly less toxic than the parent compound, especially to the kidney.
