Abstract
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 AUC0–∞ was observed in the CYP2D6*10/*10 group compared with the CYP2D6*wt/*wt group, whereas a 3.59-fold increase in AUC0–∞ was observed in CYP2C19PMs compared to CYP2C19EMs. Smokers had a 38.5% decrease in AUC0–∞ when compared to non-smokers. When these effects were combined, CYP2D6*10/*10-CYP2C19PM-Non-smokers had a 25.9-fold increase in AUC0–∞ compared to CYP2D6*wt/*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.
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Acknowledgements
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2019R1A2C1004582) and the grant from the Ministry of Food and Drug Safety of Korea.
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Byeon, JY., Cho, C., Kang, P. et al. Effects of CYP2D6 and CYP2C19 genetic polymorphisms and cigarette smoking on the pharmacokinetics of tolperisone. Arch. Pharm. Res. 46, 713–721 (2023). https://doi.org/10.1007/s12272-023-01462-1
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DOI: https://doi.org/10.1007/s12272-023-01462-1