Abstract：
Aim: This study investigated the impact of food intake and circadian rhythms on the pharmacokinetics of mavacamten. Materials & methods: A sensitive bioanalytical method for quantifying mavacamten in rat plasma was developed and validated. This method was applied to assess the effect of chronopharmacology and food intake on the pharmacokinetics of mavacamten in rats. Results: A circadian variation at two doses resulted in significant changes in the volume of distribution, clearance and time of maximum plasma concentration of mavacamten (p < 0.05). In addition, food intake had an insignificant impact on the pharmacokinetic parameters except for the time of maximum plasma concentration (p < 0.05). Conclusion: These pharmacokinetic changes and human chronotype findings will help optimize dosing time.
摘要：
目的：本研究调查了食物摄入和昼夜节律对mavacamten药代动力学的影响。材料与方法：开发并验证了一种用于定量大鼠血浆中mavacamten的灵敏生物分析方法。该方法用于评估时间药理学和食物摄入对大鼠mavacamten药代动力学的影响。结果：两个剂量的昼夜节律变化导致分布体积的显着变化，mavacamten的最大血浆浓度的清除率和时间（p<0.05）。此外,食物摄入对药代动力学参数影响不显著,但最大血浆浓度时间除外(p<0.05).结论：这些药代动力学变化和人类时间型发现将有助于优化给药时间。
