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.

中文翻译：

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两性霉素B脂质体大鼠急性毒性、毒代动力学和组织分布的性别差异

两性霉素 B (AmB) 是一种有效的多烯药物，具有广谱抗真菌活性，用于严重的真菌感染。脂质体两性霉素 B (LAmB) 是一种脂质剂型，与传统的两性霉素 B 脱氧胆酸盐 (DAmB) 相比，其毒性特征显着改善。本研究的重点是验证LAmB急性毒性的性别差异并进一步探讨其原因。在大鼠中进行LAmB和DAmB的急性毒性研究，观察并记录不同性别的毒性反应和死亡率。大鼠血浆和组织中的 AmB 浓度通过经过充分验证的 UPLC-MS/MS 分析确定。结果表明，LAmB在急性毒性方面表现出显着的性别差异，不同剂量的雌性大鼠毒性症状更严重，死亡率更高，但在相同条件下未观察到 DAmB 的相同差异。为了探究差异的原因，进行了毒代动力学和组织分布研究，结果表明与雄性大鼠相比，雌性动物具有更高的药物暴露量、更长的半衰期和更低的血浆清除率，并且药物主要分布在肝脏和肾脏中。 ，其中雌性大鼠的浓度显着高于雄性大鼠。