School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
College of Pharmacy, Dankook University, Cheonan, 31116, Republic of Korea.
Arch Pharm Res. 2023 Aug;46(8):713-721. doi: 10.1007/s12272-023-01462-1. Epub 2023 Sep 20.
Tolperisone, a muscle relaxant used for post-stroke spasticity, is metabolized to its main metabolite by CYP2D6 and to a lesser extent by CYP2C19 and CYP1A2. We investigated the effects of CYP2D6 and CYP2C19 genetic polymorphisms and cigarette smoking on tolperisone pharmacokinetics. A 150 mg oral dose of tolperisone was given to 184 healthy Korean subjects and plasma concentrations of tolperisone were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A 3.14-fold significant increase in AUC was observed in the CYP2D6*10/10 group compared with the CYP2D6wt/wt group, whereas a 3.59-fold increase in AUC was observed in CYP2C19PMs compared to CYP2C19EMs. Smokers had a 38.5% decrease in AUC when compared to non-smokers. When these effects were combined, CYP2D610/10-CYP2C19PM-Non-smokers had a 25.9-fold increase in AUC compared to CYP2D6wt/*wt-CYP2C19EM-Smokers. Genetic polymorphisms of CYP2D6 and CYP2C19 and cigarette smoking independently and significantly affected tolperisone pharmacokinetics and these effects combined resulted in a much greater impact on tolperisone pharmacokinetics.
托培酮是一种用于中风后痉挛的肌肉松弛剂，主要通过 CYP2D6 代谢为其主要代谢物，其次是 CYP2C19 和 CYP1A2。我们研究了 CYP2D6 和 CYP2C19 遗传多态性和吸烟对托培酮药代动力学的影响。184 名健康韩国受试者口服 150mg 托培酮，采用液相色谱-串联质谱法（LC-MS/MS）测定托培酮的血浆浓度。与 CYP2D6*wt/wt 组相比，CYP2D610/10 组的 AUC 增加了 3.14 倍，而 CYP2C19PM 组的 AUC 增加了 3.59 倍。与不吸烟者相比，吸烟者的 AUC 降低了 38.5%。当这些影响结合在一起时，与 CYP2D6wt/wt-CYP2C19EM-吸烟者相比，CYP2D610/*10-CYP2C19PM-不吸烟者的 AUC 增加了 25.9 倍。CYP2D6 和 CYP2C19 的遗传多态性以及吸烟独立且显著影响了托培酮的药代动力学，这些影响的结合对托培酮的药代动力学产生了更大的影响。
