The pharmacogenetics of natural products: A pharmacokinetic and pharmacodynamic perspective

Natural products have represented attractive alternatives for disease prevention and treatment over the course of human history and have contributed to the development of modern drugs. These natural products possess beneficial efficacies as well as adverse efffects, which vary largely among individuals because of genetic variations in their pharmacokinetics and pharmacodynamics. As with other synthetic chemical drugs, the dosing of natural products can be optimized to improve efficacy and reduce toxicity according to the pharmacogenetic properties. With the emergence and development of pharmacogenomics, it is possible to discover and identify the targets/mechanisms of pharmacological effects and therapeutic responses of natural products effectively and efficiently on the whole genome level. This review covers the effects of genetic variations in drug metabolizing enzymes, drug transporters, and direct and indirect interactions with the pharmacological targets/pathways on the individual response to natural products, and provides suggestions on dosing regimen adjustments of natural products based on their pharmacokinetic and pharmacogenetic paratmeters. Finally, we provide our viewpoints on the importance and necessity of pharmacogenetic and pharmacogenomic research of natural products in natural medicine's rational development and clinical application of precision medicine.