Pharmacology and toxicology of a liposomal formulation of amphotericin B (AmBisome) in rodents
| Autor: | Richard T. Proffitt, Layla Sullivan, Jill Adler-Moore, Alan Satorius, Su-Ming Chiang |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Microbiology (medical)
Spleen Pharmacology Median lethal dose Dosage form Toxicology Lethal Dose 50 chemistry.chemical_compound Mice Pharmacokinetics Amphotericin B medicine Animals Pharmacology (medical) Kidney Drug Carriers Cholesterol business.industry Rats Inbred Strains Rats Mice Inbred C57BL Infectious Diseases medicine.anatomical_structure Freeze Drying chemistry Toxicity Liposomes Phosphatidylcholines Female business medicine.drug |
| Zdroj: | The Journal of antimicrobial chemotherapy. 28 |
| ISSN: | 0305-7453 |
| Popis: | AmBisome is a lyophilized preparation of liposomal amphotericin B. The acute intravenous toxicity of AmBisome was evaluated in mice and rats, and the LD50S were found to be greater than 175 and 50 mg/kg, respectively. The corresponding LD50S for conventional amphotericin B were approximately 2.3 and 1.6 mg/kg for mice and rats, respectively. The multiple dose toxicity test confirmed that AmBisome was well tolerated by both species. There were no deaths observed among mice receiving 25 or 50 mg/kg AmBisome for 14 days, and only two deaths among mice receiving 75 mg/kg AmBisome. One rat died in the group receiving 25 mg/kg AmBisome for 30 days. However, five of ten and nine of ten rats died in the groups treated with 50 and 75 mg/kg AmBisome, respectively. Hepatotoxicity was evident by elevation in serum liver enzyme levels for these groups. Initial pharmacokinetic evaluations demonstrated that peak plasma concentrations of 87 and 118 mg/kg, respectively, were attained in mice and rats after injection with 5 mg/kg AmBisome. Terminal plasma half-lives of 3.36 and 7.56 h were calculated for mice and rats, respectively. Tissue accumulations of amphotericin B resulting from multiple dose intravenous administration of either conventional amphotericin B or AmBisome were determined. At equivalent doses of 1 mg/kg, AmBisome treatment resulted in higher liver and spleen uptake of drug, but lower kidney and lung uptake than amphotericin B. At 5 mg/kg, AmBisome treatment resulted in concentrations of drug in the kidney and lungs that were comparable to corresponding tissue levels observed in the group treated with 1 mg/kg conventional amphotericin B.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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