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.
Graphical abstract
Keywords:
- chronopharmacokinetics
- food effect
- hypertrophic cardiomyopathy
- LC-QqQ-MS
- mavacamten
- MYK-461