1. Gender differences in acute toxicity, toxicokinetic and tissue distribution of amphotericin B liposomes in rats
- Author
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Yan-Fang Xu, Jin-Long Qi, Dong Wang, Lu-Jia Wang, Wei Zhang, Hailin Zhang, Ru-Yu Huang, and Jie-Xi Ju
- Subjects
0301 basic medicine ,Drug ,Male ,Antifungal Agents ,media_common.quotation_subject ,Pharmacology ,Toxicology ,Kidney ,Dosage form ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Sex Factors ,Tandem Mass Spectrometry ,Amphotericin B ,Amphotericin B deoxycholate ,medicine ,Toxicity Tests, Acute ,Toxicokinetics ,Animals ,Tissue Distribution ,Tissue distribution ,Chromatography, High Pressure Liquid ,media_common ,business.industry ,General Medicine ,Acute toxicity ,030104 developmental biology ,Liver ,Toxicity ,Female ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Amphotericin B (AmB), an effective polyene drug with broad spectrum antifungal activity, is used for serious fungal infections. Liposomal amphotericin B (LAmB) is a lipid dosage form, which has a significantly improved toxicity profile compared with conventional amphotericin B deoxycholate (DAmB). This study focused on verifying the gender differences in the acute toxicity of LAmB and further exploring its causes. Acute toxicity study of LAmB and DAmB were performed in rats, and toxicity responses and mortality of different sexes were observed and recorded. Concentrations of AmB in rat plasma and tissues were determined by a fully validated UPLC-MS/MS assay. The results demonstrated that LAmB showed significant gender differences in acute toxicity, with more severe toxic symptoms and higher mortality for female rats at different doses, but the same differences were not observed for DAmB under the same condition. To explore the cause of differences, toxicokinetic and tissue distribution studies were performed and the results showed that female animals had higher drug exposure, longer half-life and lower plasma clearance compared to male rats, and the drug was mostly distributed in the liver and kidneys, in which female rats displayed a significant higher concentration than that of male rats.
- Published
- 2020