Effect of chronopharmacology and food on in vivo pharmacokinetic profile of mavacamten.

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.

Green bioanalysis: an innovative and eco-friendly approach for analyzing drugs in biological matrices.

Green bioanalytical techniques aim to reduce or eliminate the hazardous waste produced by bioanalytical technologies. A well-organized and practical approach towards bioanalytical method development has an enormous contribution to the green analysis. The selection of the appropriate sample extraction process, organic mobile phase components and separation technique makes the bioanalytical method green. UHPLC-MS is the best option, whereas supercritical fluid chromatography is one of the most effective green bioanalytical procedures. Nevertheless, there remains excellent scope for further research on green bioanalytical methods. This review details the various sample preparation techniques that follow green analytical chemistry principles. Furthermore, it presents green solvents as a replacement for conventional organic solvents and highlights the strategies to convert modern analytical techniques to green methods.

Cytochrome P450 enzymes: a review on drug metabolizing enzyme inhibition studies in drug discovery and development.

Assessment of drug candidate's potential to inhibit cytochrome P450 (CYP) enzymes remains crucial in pharmaceutical drug discovery and development. Both direct and time-dependent inhibition of drug metabolizing CYP enzymes by the concomitant administered drug is the leading cause of drug-drug interactions (DDIs), resulting in the increased toxicity of the victim drug. In this context, pharmaceutical companies have grown increasingly diligent in limiting CYP inhibition liabilities of drug candidates in the early stages and examining risk assessments throughout the drug development process. This review discusses different strategies and decision-making processes for assessing the drug-drug interaction risks by enzyme inhibition and lays particular emphasis on in vitro study designs and interpretation of CYP inhibition data in a stage-appropriate context.

Pharmacokinetic drug-drug interactions: an insight into recent US FDA-approved drugs for prostate cancer.

Pharmacokinetic drug-drug interaction is a significant safety and efficiency concern as it results in considerable concentration changes. Drug-drug interactions are a substantial concern in anticancer drugs that possess a narrow therapeutic index. These interactions remain as the principal regulatory obstacle that can lead to termination in the preclinical stage, restrictions in the prescription, dosage adjustments or withdrawal of the drugs from the market. Drug metabolizing enzymes or transporters mediate the majority of clinically relevant drug interactions. Cancer diagnosed aged patients use multiple medications and are more prone to significant drug-drug interactions. This review provides detailed information on clinically relevant drug-drug interactions resulting from drug metabolism by enzymes and transporters with a particular emphasis on recent FDA approved antiprostate cancer drugs.