4.5 Article

Gender differences in acute toxicity, toxicokinetic and tissue distribution of amphotericin B liposomes in rats

期刊

TOXICOLOGY LETTERS
卷 338, 期 -, 页码 78-84

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2020.12.004

关键词

Amphotericin B liposome; Acute toxicity; Toxicokinetic; UPLC-MS/MS; Gender differences; Tissue distribution

资金

  1. Natural Science Foundation of Hebei province [H2019206219]
  2. Science and Technology Key Program of Hebei Education Department [ZD2019054]
  3. Foundation of Hebei Medical University [CYCZ201901, 2020TXZH02]
  4. Hebei Province Key RD Program [19272605D]

向作者/读者索取更多资源

The study showed significant gender differences in acute toxicity of lipid dosage form amphotericin B, with more severe toxic symptoms and higher mortality observed in female rats compared to male rats. These differences may be attributed to higher drug exposure, longer half-life, lower plasma clearance, and higher drug concentrations in the liver and kidneys of female animals.
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. (C) 2020 Elsevier B.V. All rights reserved.

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