| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Acute Exposure/ On the corneas of rabbits even 0.0025% /of amphotericin B/ disrupts the epithelial cells, and 1% causes extensive damage to these cells and markedly delays healing of epithelial defects. When more than 5 mg are injected subconjunctivally, a severe local reaction results with permanent yellow discoloration of the conjunctiva and formation of raised nodules that are slow in resolving. Injected into the anterior chamber in rabbits, 0.5 mg severely damaged the corneal endothelium, but 25 ug or 50 ug did not. When injected into the vitreous body in rabbits, some investigators report 5 to 10 ug to be non toxic, while others have reported inflammation, cataract and retinal detachment and necrosis from as little as 1 or 2 ug.[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 96]/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The embryotoxic action of amphotericin B and its methyl derivative was compared in rats after their iv and intraamniotic administration. The concn of amphotericin B and its methyl derivative in the amniotic cavity on days 13, 14 and 15 of pregnancy were 1.5 and 36 ug/mL, respectively. When administered iv during the preimplantation period the antibiotics had no embryotoxic action. Iv administration of amphotericin B in a dose of 500 ug/kg and its derivative in a dose of 2000 ug/kg during organ genesis induced a decrease in the craniocaudal size. In a dose of 3000 ug/kg administered iv the methyl derivative of amphotericin B induced an increase in postimplantation death rates. Administration of amphotericin B to the amniotic cavity had no damaging action. Administration of the methyl derivative on day 15 of pregnancy led to anomalous development of the lower extremities and slower ossification. The threshold doses by the embryotoxic action for iv administration are 500 ug/kg for amphotericin B and 2000 ug/kg for the methyl derivative. Administration of the antibiotics to the amniotic cavity revealed potential teratogenic properties of the amphotericin B methyl derivative.[Moguchenok EAAntibiot Khimioter 37 (3): 25-8 (1992)]/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Studies in male and female rats using amphotericin B lipid complex at doses up to 0.32 times the usual human dose (based on body surface area) indicate that the drug does not affect fertility. When liposomal amphotericin was administered to rats in 10- or 15-mg/kg doses (equivalent to human doses of 1.6 or 2.4 mg/kg based on body surface area), there was evidence of an abnormal estrous cycle (prolonged diestrus) and decreased number of corpora lutea in female rats receiving the higher dosage but no effect on fertility or days to copulationthere were no effects on male reproductive function.[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 539]/LABORATORY ANIMALS: Neurotoxicity/ The intracisternal administration of amphotericin B and its mono-methyl ester derivative, via direct intraventricular injection (0.01 to 5 mg/ml, 6 ul) in adult female Wistar rats, revealed that amphotericin B was significantly more toxic than amphotericin B mono-methyl ester, as measured by wt loss, lethargy, death, and central nervous system histopathology. Light and electron microscopy confirmed a greater neurotoxicity for amphotericin B, manifested as edema and modest gliosis extending along and beyond the injection tract. Neuronal degeneration and myelin damage were present in amphotericin B treated (1 mg/mL) animals but were present only modestly in animals treated with amphotericin B mono methyl ester at a fivefold greater concn. Iv administration of amphotericin B to adult female Wistar rats as five daily doses of 5 mg/kg of body wt resulted in significant wt loss and some deaths. Histopathologic examination of the brains, spinal cords, and sural nerves of surviving animals revealed neurotoxicity manifested by neuronal degeneration, gliosis, and myelin edema. In sharp contrast, similar treatment with amphotericin B mono methyl ester at a 10 fold greater dose resulted in neither death nor significant neurotoxicity. The administration of five daily doses of a mixture of amphotericin B mono methyl ester-amphotericin B (9:1wt/wt) at 50 mg/kg of body wt resulted in neurotoxicity. These results indicate that amphotericin B exhibits significantly greater in vivo neurotoxicity than amphotericin B mono methyl ester.[Reuhl KR et alAntimicrob Agents Chemother 37 (3): 419-28 (1993)]For more Non-Human Toxicity Excerpts (Complete) data for AMPHOTERICIN B (6 total), please visit the HSDB record page. |
|---|
