Department of Laboratory Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.
Department of Clinical Pharmacology and Toxicology, Korea University College of Medicine, Seoul, Korea.
J Clin Pharm Ther. 2021 Dec;46(6):1659-1664. doi: 10.1111/jcpt.13507. Epub 2021 Aug 6.
Age and gender have been reported to play a crucial role in modulating the disposition of pharmacological agents, and to influence the activities of cytochrome P450 (CYP) 2D6, a drug-metabolizing enzyme involved in the disposition of clinically used drugs. In the present study, the effects of age and gender on the CYP2D6 activity were evaluated using dextromethorphan as a probe drug in humans.
Healthy young (20 < age < 30 years, n = 60) and old age (age >60 years, n = 60) subjects were enrolled and were given 15 mg dextromethorphan orally. Blood samples were collected before and 3 h after medication. Dextromethorphan and its metabolite dextrorphan were measured using HPLC-fluorescence, and dextromethorphan metabolic ratio (MR, log [dextromethorphan/dextrorphan]) was used to evaluate the CYP2D6 activity.
Mean (±SD) dextromethorphan MR was -2.42 ± 0.46 for the young male group, -2.28 ± 0.56 for the young female group, -2.46 ± 0.55 for the older male group and -2.34 ± 0.65 for the old female group. Based on our findings, the effects of age and gender on CYP2D6 activity were not statistically significant.
The results of the present study indicate that age and gender play a minor role in the modulation of CYP2D6 activity in the Korean population.
年龄和性别已被报道在调节药物处置方面起着关键作用，并影响细胞色素 P450（CYP）2D6 的活性，CYP2D6 是一种参与临床用药处置的药物代谢酶。在本研究中，我们使用右美沙芬作为探针药物，在人体中评估了年龄和性别对 CYP2D6 活性的影响。
纳入健康的年轻（<30 岁，n=60）和老年（>60 岁，n=60）受试者，并给予 15mg 右美沙芬口服。在用药前和用药后 3 小时采集血样。使用 HPLC-荧光法测定右美沙芬及其代谢产物右啡烷，并使用右美沙芬代谢比（MR，log [右美沙芬/右啡烷]）评估 CYP2D6 活性。
年轻男性组、年轻女性组、老年男性组和老年女性组的右美沙芬 MR 均值（±SD）分别为-2.42±0.46、-2.28±0.56、-2.46±0.55 和-2.34±0.65。根据我们的发现，年龄和性别对 CYP2D6 活性的影响无统计学意义。
本研究结果表明，年龄和性别在韩国人群中对 CYP2D6 活性的调节作用较小。
