Effects of CYP2C19 variants on the metabolism of tapentadol in vitro | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 15، دوره 25، شماره 5، مرداد 2022، صفحه 659-663 اصل مقاله (490.48 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2022.56996.12710 | ||
| نویسندگان | ||
| Ren-ai Xu* 1؛ Ping Fang2؛ Zhize Ye3؛ Mingming Han3؛ Jian-Ping Cai4؛ Guoxin Hu3 | ||
| 1The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China | ||
| 2The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China | ||
| 3School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China | ||
| 4The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, China | ||
| چکیده | ||
| Objective(s): This study aims to evaluate the catalytic activities of 31 CYP2C19 alleles and their effects on the metabolism of tapentadol in vitro. Materials and Methods: Insect microsomes expressing the CYP2C19 alleles were incubated with 50–1250 μM tapentadol for 40 min at 37 °C and terminated by cooling to -80 °C, immediately. Tapentadol and N-desmethyl tapentadol were analyzed by a UPLC-MS/MS system. The kinetic parameters Km, Vmax, and intrinsic clearance (Vmax/Km) of N-desmethyl tapentadol were determined. Results: As a result, the intrinsic clearance (Vmax/Km) values of most variants were significantly altered, while CYP2C19.3 and 35FS had no detectable enzyme activity. Only one variant, N277K, showed no significant difference from CYP2C19.1B. Two variants CYP2C19.29 and L16F displayed markedly increased intrinsic clearance values of 302.22% and 199.97%, respectively; whereas 24 variants exhibited significantly decreased relative clearance ranging from 0.32% to 79.15% of CYP2C19.1B. Especially, CYP2C19.2G, 2H, R124Q, and R261W exhibited a drastic decrease in clearance (>80%) compared with wild-type CYP2C19.1B. Conclusion: As the first study of all aforementioned alleles for tapentadol metabolism, the comprehensive data in vitro may provide novel insights into the allele-specific and substrate-specific activity of CYP2C19. | ||
| کلیدواژهها | ||
| Cytochrome P450؛ CYP2C19 variants؛ Drug metabolism؛ Genetic polymorphism؛ Tapentadol | ||
| مراجع | ||
|
1. Liu JP, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev 2009; 41:289-295. 2. Wang B, Wang J, Huang SQ, Su HH, Zhou SF. Genetic polymorphism of the human cytochrome P450 2C9 gene and its clinical significance. Curr Drug Metab 2009; 10:781-834. 3. Hiratsuka M. In vitro assessment of the allelic variants of cytochrome P450. Drug Metab Pharmacokinet 2012; 27:68-84. 4. Zanger UM, Turpeinen M, Klein K, Schwab M. Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal Bioanal Chem 2008; 392:1093-1108. 5. Rendic S. Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev 2002; 34:448-483. 6. Desta Z, Zhao X, Shin JG, Flockhart DA. Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet 2002; 41:913-958. 7. Ono S, Hatanaka T, Miyazawa S, Tsutsui M, Aoyama T, Gonzalez FJ, et al. Human liver microsomal diazepam metabolism using cDNA-expressed cytochrome P450s: role of CYP2B6, 2C19 and the 3A subfamily. Xenobiotica 1996; 26:1155-1166. 8. Hu LM, Dai DP, Hu GX, Yang JF, Xu RA, Yang LP, et al. Genetic polymorphisms and novel allelic variants of CYP2C19 in the Chinese Han population. Pharmacogenomics 2012; 13:1571-1581. 9. Dai DP, Hu LM, Geng PW, Wang SH, Cai J, Hu GX, et al. In vitro functional analysis of 24 novel CYP2C19 variants recently found in the Chinese Han population. Xenobiotica 2015; 45:1030-1035. 10. Hartrick CT. Tapentadol immediate release for the relief of moderate-to-severe acute pain. Expert Opin Pharmacother 2009; 10:2687-2696. 11. Kress HG. Tapentadol and its two mechanisms of action: is there a new pharmacological class of centrally-acting analgesics on the horizon? Eur J Pain 2010; 14:781-783. 12. Barbosa J, Faria J, Queiros O, Moreira R, Carvalho F, Dinis-Oliveira RJ. Comparative metabolism of tramadol and tapentadol: a toxicological perspective. Drug Metab Rev 2016; 48:577-592. 13. Comelon M, Raeder J, Draegni T, Lieng M, Lenz H. Tapentadol versus oxycodone analgesia and side effects after laparoscopic hysterectomy: a randomised controlled trial. Eur J Anaesthesiol 2021; 38:995-1002. 14. Mateos RG, Bernal DS, Morera LMT, Ferri CM, Escobar AE. Long-term effectiveness and tolerability of pain treatment with tapentadol prolonged release. Pain Physician 2021; 24:75-85. 15. Knezevic NN, Tverdohleb T, Knezevic I, Candido KD. Unique pharmacology of tapentadol for treating acute and chronic pain. Expert Opin Drug Metab Toxicol 2015; 11:1475-1492. 16. Terlinden R, Ossig J, Fliegert F, Lange C, Gohler K. Absorption, metabolism, and excretion of 14C-labeled tapentadol HCl in healthy male subjects. Eur J Drug Metab Pharmacokinet 2007; 32:163-169. 17. Terlinden R, Kogel BY, Englberger W, Tzschentke TM. In vitro and in vivo characterization of tapentadol metabolites. Methods Find Exp Clin Pharmacol 2010; 32:31-38. 18. DePriest AZ, Puet BL, Holt AC, Roberts A, Cone EJ. Metabolism and disposition of prescription opioids: a review. Forensic Sci Rev 2015; 27:115-145. 19. Zhou XY, Hu XX, Li MF, Wang H, Zhang LQ, Hu GX, et al. Functional characterization of CYP2C19 variants in nebivolol 4-hydroxlation in vitro. Drug Test Anal 2018; 10:807-813. 20. Kneip C, Terlinden R, Beier H, Chen G. Investigations into the drug-drug interaction potential of tapentadol in human liver microsomes and fresh human hepatocytes. Drug Metab Lett 2008; 2:67-75. 21. Faria J, Barbosa J, Moreira R, Queiros O, Carvalho F, Dinis-Oliveira RJ. Comparative pharmacology and toxicology of tramadol and tapentadol. Eur J Pain 2018; 22:827-844. 22. Lan T, Yuan LJ, Hu XX, Zhou Q, Wang J, Huang XX, et al. Effects of CYP2C19 variants on methadone metabolism in vitro. Drug Testing Anal 2016; 9:634-639. 23. Hanioka N, Tsuneto Y, Saito Y, Sumada T, Maekawa K, Saito K, et al. Functional characterization of two novel CYP2C19 variants (CYP2C19*18 and CYP2C19*19) found in a Japanese population. Xenobiotica 2007; 37:342-355. 24. Jin T, Zhang X, Geng T, Shi X, Wang L, Yuan D, et al. Genotypephenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy. Mol Med Rep 2016; 13:2117-2123. 25. Hu LM, Dai DP, Hu GX, Yang JF, Xu RA, Yang LP, et al. Genetic polymorphisms and novel allelic variants of CYP2C19 in the Chinese Han population. Pharmacogenomics 2012; 13:1571-1581. 26. Tantray JA, Reddy KP, Jamil K, Kumar YS. Pharmacodynamic and cytogenetic evaluation in CYP2C19*2 and CYP2C19*3 allelomorphism in South Indian population with clopidogrel therapy. Int J Cardiol 2017; 229:113-118. 27. Chen L, Qin S, Xie J, Tang J, Yang L, Shen W, et al. Genetic polymorphism analysis of CYP2C19 in Chinese Han populations from different geographic areas of mainland China. Pharmacogenomics 2008; 9:691-702. 28. Chen M, Liu XJ, Yan SD, Peng Y, Chai H, Li Q, et al. Association between cytochrome P450 2C19 polymorphism and clinical outcomes in Chinese patients with coronary artery disease. Atherosclerosis 2012; 220:168-171. 29. De Morais SM, Wilkinson GR, Blaisdell J, Meyer UA, Nakamura K, Goldstein JA. Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol 1994; 46:594-598. 30. de Morais SM, Goldstein JA, Xie HG, Huang SL, Lu YQ, Xia H, et al. Genetic analysis of the S-mephenytoin polymorphism in a Chinese population. Clin Pharmacol Ther 1995; 58:404-411. 31. Rosemary J, Adithan C. The pharmacogenetics of CYP2C9 and CYP2C19: ethnic variation and clinical significance. Curr Clin Pharmacol 2007; 2:93-109. | ||
|
آمار تعداد مشاهده مقاله: 401 تعداد دریافت فایل اصل مقاله: 254 |
||