Effect of Chronopharmacology and Food on in Vivo Pharmacokinetic Profile of Mavacamten

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.

Graphical abstract

Keywords:

• chronopharmacokinetics
• food effect
• hypertrophic cardiomyopathy
• LC-QqQ-MS
• mavacamten
• MYK-461

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.4155/bio-2023-0030

Author contributions

SNR Gajula and R Sonti contributed to the study plan, method development and validation, analysis, data interpretation and manuscript writing. S Talari and T N Nathani prepared the samples and the manuscript draft. V Munjal prepared the samples. Z Rahman and MP Dandeka executed the dosing, blood collection and manuscript correction. All authors read and approved the final manuscript.

Ethical conduct of research

The animal experiments were duly approved by the Institutional Animal Ethics Committee of National Institute of Pharmaceutical Education & Research, Hyderabad, India (approval no. NIP/12/2022/PAA/444), and all the experiments carried out as per the Committee for Control and Supervision of Experiments on Animals guidelines of the government of India. All animal procedures were conducted under institutional-approved Animal Care and Use Committee protocols.

Acknowledgments

The authors are grateful to the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India, New Delhi, for the National Institute of Pharmaceutical Education and Research (NIPER) fellowship award. The authors thank Dr Chandraiah Godugu for his valuable suggestion in this research work. The manuscript bears the NIPER-Hyderabad communication no. NIPERHYD/2022/137.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2144/000112170