Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Jung-In Park, Choon-Gon Jang, Seok-Yong Lee, Chang-Ik Choi, Jung‑Woo Bae, Yun Jeong Lee
{"title":"CYP2D6*10等位基因对托培里松药动学的影响","authors":"Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Jung-In Park, Choon-Gon Jang, Seok-Yong Lee, Chang-Ik Choi, Jung‑Woo Bae, Yun Jeong Lee","doi":"10.1007/s12272-022-01422-1","DOIUrl":null,"url":null,"abstract":"<div><p>Tolperisone, a muscle relaxant used for post-stroke spasticity, has been reported to have a very wide interindividual pharmacokinetic variability. It is metabolized mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. CYP2D6 is a highly polymorphic enzyme, and <i>CYP2D6*wt</i>/<i>*wt</i>, <i>CYP2D6*wt/*10</i> and <i>CYP2D6*10/*10</i> genotypes constitute more than 90% of the <i>CYP2D6</i> genotypes in the Korean population. Thus, effects of the <i>CYP2D6*10</i> on tolperisone pharmacokinetics were investigated in this study to elucidate the reasons for the wide interindividual variability. Oral tolperisone 150 mg was given to sixty-four healthy Koreans, and plasma concentrations of tolperisone were measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS). The <i>CYP2D6*10/*10</i> and <i>CYP2D6*wt/*10</i> groups had significantly higher C<sub>max</sub> and lower CL/F values than the <i>CYP2D6*wt/*wt</i> group. The AUC<sub>inf</sub> of <i>CYP2D6*10/*10</i> and <i>CYP2D6*wt/*10</i> groups were 5.18-fold and 2.25-fold higher than the <i>CYP2D6*wt/*wt</i> group, respectively. There were considerable variations in the C<sub>max</sub> and AUC values within each genotype group, and the variations were greater as the activity of CYP2D6 decreased. These results suggest that the genetic polymorphism of <i>CYP2D6</i> significantly affected tolperisone pharmacokinetics and factor(s) other than CYP2D6 may also have significant effects on the pharmacokinetics of tolperisone.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":null,"pages":null},"PeriodicalIF":6.9000,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-022-01422-1.pdf","citationCount":"3","resultStr":"{\"title\":\"Effects of CYP2D6*10 allele on the pharmacokinetics of tolperisone\",\"authors\":\"Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Jung-In Park, Choon-Gon Jang, Seok-Yong Lee, Chang-Ik Choi, Jung‑Woo Bae, Yun Jeong Lee\",\"doi\":\"10.1007/s12272-022-01422-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Tolperisone, a muscle relaxant used for post-stroke spasticity, has been reported to have a very wide interindividual pharmacokinetic variability. It is metabolized mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. CYP2D6 is a highly polymorphic enzyme, and <i>CYP2D6*wt</i>/<i>*wt</i>, <i>CYP2D6*wt/*10</i> and <i>CYP2D6*10/*10</i> genotypes constitute more than 90% of the <i>CYP2D6</i> genotypes in the Korean population. Thus, effects of the <i>CYP2D6*10</i> on tolperisone pharmacokinetics were investigated in this study to elucidate the reasons for the wide interindividual variability. Oral tolperisone 150 mg was given to sixty-four healthy Koreans, and plasma concentrations of tolperisone were measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS). The <i>CYP2D6*10/*10</i> and <i>CYP2D6*wt/*10</i> groups had significantly higher C<sub>max</sub> and lower CL/F values than the <i>CYP2D6*wt/*wt</i> group. The AUC<sub>inf</sub> of <i>CYP2D6*10/*10</i> and <i>CYP2D6*wt/*10</i> groups were 5.18-fold and 2.25-fold higher than the <i>CYP2D6*wt/*wt</i> group, respectively. There were considerable variations in the C<sub>max</sub> and AUC values within each genotype group, and the variations were greater as the activity of CYP2D6 decreased. These results suggest that the genetic polymorphism of <i>CYP2D6</i> significantly affected tolperisone pharmacokinetics and factor(s) other than CYP2D6 may also have significant effects on the pharmacokinetics of tolperisone.</p></div>\",\"PeriodicalId\":8287,\"journal\":{\"name\":\"Archives of Pharmacal Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.9000,\"publicationDate\":\"2022-12-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s12272-022-01422-1.pdf\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Pharmacal Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s12272-022-01422-1\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Pharmacal Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12272-022-01422-1","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Effects of CYP2D6*10 allele on the pharmacokinetics of tolperisone
Tolperisone, a muscle relaxant used for post-stroke spasticity, has been reported to have a very wide interindividual pharmacokinetic variability. It is metabolized mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. CYP2D6 is a highly polymorphic enzyme, and CYP2D6*wt/*wt, CYP2D6*wt/*10 and CYP2D6*10/*10 genotypes constitute more than 90% of the CYP2D6 genotypes in the Korean population. Thus, effects of the CYP2D6*10 on tolperisone pharmacokinetics were investigated in this study to elucidate the reasons for the wide interindividual variability. Oral tolperisone 150 mg was given to sixty-four healthy Koreans, and plasma concentrations of tolperisone were measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS). The CYP2D6*10/*10 and CYP2D6*wt/*10 groups had significantly higher Cmax and lower CL/F values than the CYP2D6*wt/*wt group. The AUCinf of CYP2D6*10/*10 and CYP2D6*wt/*10 groups were 5.18-fold and 2.25-fold higher than the CYP2D6*wt/*wt group, respectively. There were considerable variations in the Cmax and AUC values within each genotype group, and the variations were greater as the activity of CYP2D6 decreased. These results suggest that the genetic polymorphism of CYP2D6 significantly affected tolperisone pharmacokinetics and factor(s) other than CYP2D6 may also have significant effects on the pharmacokinetics of tolperisone.
期刊介绍:
Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.