Effects of CYP2C19 genetic polymorphism on the pharmacokinetics of tolperisone in healthy subjects

• Published in: Archives of pharmacal research Vol. 46; no. 2; pp. 111 - 116
• Main Authors: Cho, Chang‑Keun, Byeon, Ji-Young, Kang, Pureum, Park, Hye-Jung, Ko, Eunvin, Mu, Chou Yen, Jang, Choon-Gon, Lee, Seok-Yong, Lee, Yun Jeong
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.02.2023; 대한약학회
• Subjects: blood; Cytochrome P-450 CYP2C19 - genetics; Cytochrome P-450 CYP2D6 - genetics; genetic polymorphism; Genotype; Healthy Volunteers; Humans; liquid chromatography; Medicine; metabolites; muscle relaxants; muscles; oral administration; pharmacokinetics; Pharmacology/Toxicology; Pharmacy; Polymorphism, Genetic; Research Article; tandem mass spectrometry; Tolperisone - pharmacokinetics; 약학; Tolperisone; Genotype; CYP2C19; Pharmacokinetics; Genetic polymorphism; Pharmacogenomics
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-022-01423-0

Tolperisone hydrochloride is a centrally-acting muscle relaxant used for relieving spasticities of neurological origin and muscle spasms associated with painful locomotor diseases. It is metabolized to the inactive metabolite mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. In our previous study, the pharmacokinetics of tolperisone was significantly affected by the genetic polymorphism of CYP2D6 , but the wide interindividual variation of tolperisone pharmacokinetics was not explained by genetic polymorphism of CYP2D6 alone. Thus, we studied the effects of CYP2C19 genetic polymorphism on tolperisone pharmacokinetics. Eighty-one subjects with different CYP2C19 genotypes received a single oral dose of 150 mg tolperisone with 240 mL of water, and blood samples were collected up to 12 h after dosing. The plasma concentration of tolperisone was measured by a liquid chromatography-tandem mass spectrometry system. The CYP2C19PM group had significantly higher C max and lower CL/F values than the CYP2C19EM and CYP2C19IM groups. The AUC inf of the CYP2C19PM group was 2.86-fold and 3.00-fold higher than the CYP2C19EM and CYP2C19IM groups, respectively. In conclusion, the genetic polymorphism of CYP2C19 significantly affected tolperisone pharmacokinetics.