Effect of chronopharmacology and food on in vivo pharmacokinetic profile of mavacamten: supplementary materials

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. Thismethod 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 ofmaximum 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.