Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, PR China; Institute of Clinical Pharmacology, Central South University, Changsha, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, PR China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, PR China.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, PR China; Institute of Clinical Pharmacology, Central South University, Changsha, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, PR China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, PR China.
Pharmacol Res. 2019 Aug;146:104283. doi: 10.1016/j.phrs.2019.104283. Epub 2019 May 23.
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.
天然产物作为疾病预防和治疗的手段，在人类历史上一直具有吸引力，并为现代药物的发展做出了贡献。这些天然产物具有有益的疗效和不良的作用，由于个体在药代动力学和药效动力学方面存在遗传变异，因此差异很大。与其他合成化学药物一样，根据药物遗传学特性，可以优化天然产物的剂量，以提高疗效和降低毒性。随着药物基因组学的出现和发展，有可能在全基因组水平上有效地发现和识别天然产物的药理作用和治疗反应的靶标/机制。本综述涵盖了药物代谢酶、药物转运体以及与药理靶标/途径的直接和间接相互作用的遗传变异对个体对天然产物反应的影响，并根据其药代动力学和药物遗传学参数，为天然产物的剂量方案调整提供了建议。最后，我们就天然产物的药物遗传学和药物基因组学研究在天然药物的合理发展和精准医学的临床应用中的重要性和必要性提出了我们的观点。
