RESUMO
Nadolol, a beta-adrenergic antagonist, and bendroflumethiazide, a thiazide diuretic, were administered orally alone and in combination to animals in acute and 6-month toxicity studies and in a rat teratology study. The two drugs in combination showed no evidence of potentiation of acute toxicity in mice. Nadolol and/or bendroflumethiazide were administered orally to rats at daily doses of 1000 or 160 mg/kg of nadolol and 125 or 20 mg/kg of bendroflumethiazide and to dogs at daily doses of 160 or 40 mg/kg of nadolol and 20 or 5 mg/kg of bendroflumethiazide for 6 months. The two drugs, alone and in combination, caused only minor changes in clinical-laboratory tests and no major gross or histopathologic changes. Many of the changes noted were expected pharmacologic effects of the individual agents. The drugs, alone or in combination, produced no evidence of embryotoxicity, fetotoxicity, or teratogenicity in rats. The results of these studies indicate that nadolol and bendroflumethiazide have a low order of toxicity individually, and when given in combination show no additional or potentiated toxicity.
Assuntos
Bendroflumetiazida/toxicidade , Propanolaminas/toxicidade , Animais , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Cães , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Eletrólitos/sangue , Feminino , Frequência Cardíaca/efeitos dos fármacos , Dose Letal Mediana , Masculino , Camundongos , Nadolol , Gravidez , Ratos , Especificidade da Espécie , Teratogênicos , Equilíbrio Hidroeletrolítico/efeitos dos fármacosAssuntos
Antibacterianos/toxicidade , Animais , Aztreonam , Ceco/efeitos dos fármacos , Cães , Feminino , Coração/efeitos dos fármacos , Injeções Intravenosas , Injeções Subcutâneas , Rim/efeitos dos fármacos , Dose Letal Mediana , Fígado/efeitos dos fármacos , Masculino , Camundongos , Ratos , Fatores de Tempo , beta-Lactamas/toxicidadeAssuntos
Antagonistas Adrenérgicos beta/toxicidade , Propanolaminas/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Carcinógenos , Cricetinae , Cães , Feminino , Teste de Tolerância a Glucose , Haplorrinos , Macaca mulatta , Masculino , Mesocricetus , Camundongos , Gravidez , Coelhos , Ratos , Reprodução/efeitos dos fármacos , Especificidade da Espécie , Teratogênicos , Fatores de TempoRESUMO
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.