Han Chinese specific cytochrome P450 polymorphisms and their impact on the metabolism of anti-hypertensive drugs with adrenoreceptor blocking properties

References

• Samer CF, Lorenzini KI, Rollason V, et al. Applications of CYP450 testing in the clinical setting. Mol Diagn Ther. 2013;17(3):165–184.
   PubMed Web of Science ®Google Scholar
• Deodhar M, Al Rihani SB, Arwood MJ, et al. Mechanisms of CYP450 inhibition: understanding drug-drug interactions due to mechanism-based inhibition in clinical practice. Pharmaceutics. 2020 Sep 4;12(9):846.
   PubMed Web of Science ®Google Scholar
• Iyer KR, Sinz MW. Characterization of Phase I and Phase II hepatic drug metabolism activities in a panel of human liver preparations. Chem Biol Interact. 1999 Apr 1;118(2):151–169.
   PubMed Web of Science ®Google Scholar
• Zanger UM, Cytochrome SM. P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Therapeut. 2013 Apr;138(1):103–141.
   PubMed Web of Science ®Google Scholar
• Hoffman JM, Dunnenberger HM, Hicks JK, et al. Developing knowledge resources to support precision medicine: principles from the Clinical Pharmacogenetics Implementation Consortium (CPIC). J Am Med Inform Assn. 2016 Jul;23(4):796–801.
   PubMed Web of Science ®Google Scholar
• Ingelman-Sundberg M, Sim SC, Gomez A, et al. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Therapeut. 2007 Dec;116(3):496–526.
   PubMed Web of Science ®Google Scholar
• Brewer CT, Chen TS. Hepatotoxicity of herbal supplements mediated by modulation of cytochrome P450. Int J Mol Sci. 2017 Nov;18(11):2353.
   PubMed Web of Science ®Google Scholar
• Gervasini G, Benitez J, Carrillo JA. Pharmacogenetic testing and therapeutic drug monitoring are complementary tools for optimal individualization of drug therapy. Eur J Clin Pharmacol. 2010 Aug;66(8):755–774.
   PubMed Web of Science ®Google Scholar
• Caudle KE, Dunnenberger HM, Freimuth RR, et al. Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC). Genet Med. 2017 Feb;19(2):215–223.
   PubMed Web of Science ®Google Scholar
• Relling MV, Klein TE, Gammal RS, et al. The clinical pharmacogenetics implementation consortium: 10 years later. Clin Pharmacol Ther. 2020 Jan;107(1):171–175.
   PubMed Web of Science ®Google Scholar
• Polimanti R, Piacentini S, Manfellotto D, et al. Human genetic variation of CYP450 superfamily: analysis of functional diversity in worldwide populations. Pharmacogenomics. 2012 Dec;13(16):1951–1960.
   PubMed Web of Science ®Google Scholar
• Johansson I, Ingelman-Sundberg M. Genetic polymorphism and toxicology-with emphasis on cytochrome P450. Toxicol Sci. 2011 Mar;120(1):1–13.
   PubMed Web of Science ®Google Scholar
• Zhou SF, Liu JP, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev. 2009 May;41(2):89–295.
   PubMed Web of Science ®Google Scholar
• McGraw J, Cytochrome WD. P450 variations in different ethnic populations. Expert Opin Drug Met. 2012 Mar;8(3):371–382.
   PubMed Web of Science ®Google Scholar
• Tracy TS, Chaudhry AS, Prasad B, et al. Interindividual variability in cytochrome P450-mediated drug metabolism. Drug Metab Dispos. 2016 Mar;44(3):343–351.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Ingelman-Sundberg M, Lauschke VM. Worldwide distribution of cytochrome P450 alleles: a meta-analysis of population-scale sequencing Projects. Clin Pharmacol Ther. 2017 Oct;102(4):688–700.
   PubMed Web of Science ®Google Scholar
• Dai DP, Xu RA, Hu LM, et al. CYP2C9 polymorphism analysis in Han Chinese populations: building the largest allele frequency database. Pharmacogenomics J. 2014 Feb;14(1):85–92.
   PubMed Web of Science ®Google Scholar
• Hu LM, Dai DP, Hu GX, et al. Genetic polymorphisms and novel allelic variants of CYP2C19 in the Chinese Han population. Pharmacogenomics. 2012 Nov;13(14):1571–1581.
   PubMed Web of Science ®Google Scholar
• Qian JC, Xu XM, Hu GX, et al. Genetic variations of human CYP2D6 in the Chinese Han population. Pharmacogenomics. 2013 Nov;14(14):1731–1743.
   PubMed Web of Science ®Google Scholar
• Xie HG, Prasad HC, Kim RB, et al. CYP2C9 allelic variants: ethnic distribution and functional significance. Adv Drug Deliv Rev. 2002 Nov 18;54(10):1257–1270.
   PubMed Web of Science ®Google Scholar
• Gaedigk A, Sangkuhl K, Whirl-Carrillo M, et al. Prediction of CYP2D6 phenotype from genotype across world populations. Genet Med. 2017 Jan;19(1):69–76.
   PubMed Web of Science ®Google Scholar
• Martis S, Mei H, Vijzelaar R, et al. Multi-ethnic cytochrome-P450 copy number profiling: novel pharmacogenetic alleles and mechanism of copy number variation formation. Pharmacogenomics J. 2013 Dec;13(6):558–566.
   PubMed Web of Science ®Google Scholar
• De Leon J, Armstrong SC, Cozza KL. Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP4502C19. Psychosomatics. 2006 Feb;47(1):75–85.
   PubMed Web of Science ®Google Scholar
• Wang G, Lei HP, Li Z, et al. The CYP2C19 ultra-rapid metabolizer genotype influences the pharmacokinetics of voriconazole in healthy male volunteers. Eur J Clin Pharmacol. 2009 Mar;65(3):281–285.
   PubMed Web of Science ®Google Scholar
• Kirchheiner J, Heesch C, Bauer S, et al. Impact of the ultrarapid metabolizer genotype of cytochrome P450 2D6 on metoprolol pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2004 Oct;76(4):302–312.
   PubMed Web of Science ®Google Scholar
• Kirchheiner JC, Henckel HB, Franke L, et al. Impact of the CYP2D6 ultra-rapid metabolizer genotype on cis- and trans-doxepin pharmacokinetics and serotonin concentration in platelets. Clin Pharmacol Ther. 2005 Feb;77(2):26.
   Web of Science ®Google Scholar
• Spring MD, Sousa JC, Li QG, et al. Determination of cytochrome P450 Isoenzyme 2D6 (CYP2D6) genotypes and pharmacogenomic impact on primaquine metabolism in an active-duty US military population. J Infect Dis. 2019 Dec;220(11):1761–1770.
   PubMed Web of Science ®Google Scholar
• Theken KN, Lee CR, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and nonsteroidal anti-inflammatory drugs. Clin Pharmacol Ther. 2020 Aug;108(2):191–200.
   PubMed Web of Science ®Google Scholar
• Moriyama B, Obeng AO, Barbarino J, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and Voriconazole Therapy (vol 102, pg 45, 2017). Clin Pharmacol Ther. 2018 Feb;103(2):349.
   PubMed Web of Science ®Google Scholar
• Goetz MP, Sangkuhl K, Guchelaar HJ, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and tamoxifen therapy. Clin Pharmacol Ther. 2018 May;103(5):770–777.
   PubMed Web of Science ®Google Scholar
• Moriyama B, Obeng AO, Barbarino J, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and voriconazole therapy. Clin Pharmacol Ther. 2017 Jul;102(1):45–51.
   PubMed Web of Science ®Google Scholar
• Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017 Jul;102(1):37–44.
   PubMed Web of Science ®Google Scholar
• Bell GC, Caudle KE, Whirl-Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 genotype and use of ondansetron and tropisetron. Clin Pharmacol Ther. 2017 Aug;102(2):213–218.
   PubMed Web of Science ®Google Scholar
• Birdwell KA, Decker B, Barbarino JM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clin Pharmacol Ther. 2015 Jul;98(1):19–24.
   PubMed Web of Science ®Google Scholar
• Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther. 2012 Feb;91(2):321–326.
   PubMed Web of Science ®Google Scholar
• Noubiap JJ, Nansseu JR, Nyaga UF, et al. Global prevalence of resistant hypertension: a meta-analysis of data from 3.2 million patients. Heart. 2019 Jan;105(2):98–105.
   PubMed Web of Science ®Google Scholar
• Oparil S, Acelajado MC, Bakris GL, et al. Hypertension. Nat Rev Dis Primers. 2018;22:4.
   Google Scholar
• Iadecola C, Yaffe K, Biller J, et al. Impact of hypertension on cognitive function: a scientific statement from the american heart association. Hypertension. 2016 Dec;68(6):E67–E94.
   PubMed Web of Science ®Google Scholar
• Olsen MH, Angell SY, Asma S, et al. A call to action and a lifecourse strategy to address the global burden of raised blood pressure on current and future generations: the Lancet Commission on hypertension. Lancet. 2016 Nov 26;388(10060):2665–2712.
   PubMed Web of Science ®Google Scholar
• Zhou MG, Wang HD, Zeng XY, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019 Sep 28;394(10204):1145–1158.
   PubMed Web of Science ®Google Scholar
• Zhao D, Liu J, Wang M, et al. Epidemiology of cardiovascular disease in China: current features and implications. Nat Rev Cardiol. 2019 Apr;16(4):203–212.
   PubMed Web of Science ®Google Scholar
• Wang ZW, Chen Z, Zhang LF, et al. Status of hypertension in china results from the china hypertension survey, 2012-2015. Circulation. 2018 May 29;137(22):2344–2356.
   PubMed Web of Science ®Google Scholar
• Lu JP, Lu Y, Wang XC, et al. Prevalence, awareness, treatment, and control of hypertension in China: data from 1.7 million adults in a population-based screening study (China PEACE Million Persons Project). Lancet. 2017 Dec 9;390(10112):2549–2558.
   PubMed Web of Science ®Google Scholar
• Thomas CD, Johnson JA. Pharmacogenetic factors affecting beta-blocker metabolism and response. Expert Opin Drug Met. 2020 Sep 9;16(10):953–964.
   Web of Science ®Google Scholar
• Yuan ZQY, Zhang HW, Yu ZD, et al. Impact of 14 types of genetic polymorphisms on antihypertensive efficacy of felodipine in healthy Chinese subjects. Int J Clin Pharm Th. 2020 Jul;58(7):375–386.
   PubMed Web of Science ®Google Scholar
• Yang RR, Luo ZQ, Liu Y, et al. Drug Interactions with Angiotensin Receptor Blockers: role of Human Cytochromes P450. Curr Drug Metab. 2016;17(7):681–691.
   PubMed Web of Science ®Google Scholar
• Weeke P, Roden DM. Applied pharmacogenomics in cardiovascular medicine. Annu Rev Med. 2014;65(1):81–94.
   PubMedGoogle Scholar
• Waring RH. Cytochrome P450: genotype to phenotype. Xenobiotica. 2020 Jan 2;50(1): 9–18.
   PubMed Web of Science ®Google Scholar
• Kalman LV, Agundez JAG, Appell ML, et al. Pharmacogenetic allele nomenclature: international workgroup recommendations for test result reporting. Clin Pharmacol Ther. 2016 Feb;99(2):172–185.
   PubMed Web of Science ®Google Scholar
• Gaedigk A, Ingelman-Sundberg M, Miller NA, et al. The pharmacogene variation (PharmVar) Consortium: incorporation of the Human Cytochrome P450 (CYP) Allele Nomenclature Database. Clin Pharmacol Ther. 2018 Mar;103(3):399–401.
   PubMed Web of Science ®Google Scholar
• Rendic S. Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1–2):83–448.
   PubMed Web of Science ®Google Scholar
• Van Booven D, Marsh S, McLeod H, et al. Cytochrome P450 2C9-CYP2C9. Pharmacogenet Genomics. 2010 Apr;20(4):277–281.
   PubMed Web of Science ®Google Scholar
• Fohner AE, Robinson R, Yracheta J, et al. Variation in genes controlling warfarin disposition and response in American Indian and Alaska Native people: CYP2C9, VKORC1, CYP4F2, CYP4F11, GGCX. Pharmacogenet Genomics. 2015 Jul;25(7):343–353.
   PubMed Web of Science ®Google Scholar
• Soares RAG, Santos PCJL, Gll M-C, et al. CYP2C9 and VKORC1 polymorphisms are differently distributed in the brazilian population according to self-declared ethnicity or genetic ancestry. Genet Test Mol Bioma. 2012 Aug;16(8):957–963. .
   PubMed Web of Science ®Google Scholar
• Johnson JA, Gong L, Whirl-Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther. 2011 Oct;90(4):625–629.
   PubMed Web of Science ®Google Scholar
• Desta Z, Zhao XJ, Shin JG, et al. Clinical significance of the cytochrome P4502C19 genetic polymorphism. Clin Pharmacokinet. 2002;41(12):913–958.
   PubMed Web of Science ®Google Scholar
• Scott SA, Sangkuhl K, Gardner EE, et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450-2C19 (CYP2C19) Genotype and Clopidogrel Therapy. Clin Pharmacol Ther. 2011 Aug;90(2):328–332.
   PubMed Web of Science ®Google Scholar
• Chen LL, Qin SY, Xie J, et al. Genetic polymorphism analysis of CYP2C19 in Chinese Han populations from different geographic areas of mainland China. Pharmacogenomics. 2008 Jun;9(6):691–702.
   PubMed Web of Science ®Google Scholar
• Zuo LJ, Guo T, Xia DY, et al. Allele and genotype frequencies of CYP3A4, CYP2C19, and CYP2D6 in Han, Uighur, Hui, and Mongolian Chinese Populations. Genet Test Mol Bioma. 2012 Feb;16(2):102–108.
   PubMed Web of Science ®Google Scholar
• Chen M, Liu XJ, Yan SD, et al. Association between cytochrome P450 2C19 polymorphism and clinical outcomes in Chinese patients with coronary artery disease. Atherosclerosis. 2012 Jan;220(1):168–171.
   PubMed Web of Science ®Google Scholar
• Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance part II. Clin Pharmacokinet. 2009;48(12):761–804.
   PubMed Web of Science ®Google Scholar
• Nofziger C, Turner AJ, Sangkuhl K, et al. PharmVar GeneFocus: CYP2D6. Clin Pharmacol Ther. 2020 Jan;107(1):154–170.
   PubMed Web of Science ®Google Scholar
• Hicks JK, Swen JJ, Thorn CF, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther. 2013 May;93(5):402–408.
   PubMed Web of Science ®Google Scholar
• De Leon J, Susce MT, Johnson M, et al. DNA Microarray Technology in the Clinical Environment: the AmpliChip CYP450 Test for CYP2D6 and CYP2C19 genotyping. CNS Spectr. 2009 Jan;14(1):19–34.
   PubMed Web of Science ®Google Scholar
• Man M, Farmen M, Dumaual C, et al. Genetic variation in metabolizing enzyme and transporter genes: comprehensive assessment in 3 major East Asian subpopulations with comparison to Caucasians and Africans. J Clin Pharmacol. 2010 Aug;50(8):929–940.
   PubMed Web of Science ®Google Scholar
• Mizutani T. PM frequencies of major CYPs in Asians and Caucasians. Drug Metab Rev. 2003;35(2–3):99–106.
   PubMed Web of Science ®Google Scholar
• Neafsey P, Ginsberg G, Hattis D, et al. Genetic Polymorphism in Cytochrome P450 2d6 (Cyp2d6): population Distribution of Cyp2d6 Activity. J Toxicol Env Heal B. 2009;12(5–6):334–361.
   Google Scholar
• Wang D, Guo Y, Wrighton SA, et al. Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. Pharmacogenomics J. 2011 Aug;11(4):274–286.
   PubMed Web of Science ®Google Scholar
• Galetin A, Ito K, Hallifax D, et al. CYP3A4 substrate selection and substitution in the prediction of potential drug-drug interactions. J Pharmacol Exp Ther. 2005 Jul;314(1):180–190.
   PubMed Web of Science ®Google Scholar
• Drogemoller B, Plummer M, Korkie L, et al. Characterization of the genetic variation present in CYP3A4 in three South African populations. Front Genet. 2013;4:17.
   PubMedGoogle Scholar
• Lamba JK, Lin YS, Thummel K, et al. Common allelic variants of cytochrome P4503A4 and their prevalence in different populations. Pharmacogenetics. 2002 Mar;12(2):121–132.
   PubMedGoogle Scholar
• Hu GX, Dai DP, Wang H, et al. Systematic screening for CYP3A4 genetic polymorphisms in a Han Chinese population. Pharmacogenomics. 2017 Mar;18(4):369–379.
   PubMed Web of Science ®Google Scholar
• Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018 Oct 23;138(17):E484–E594.
   PubMed Web of Science ®Google Scholar
• Wang YH, Pan PP, Dai DP, et al. Effect of 36 CYP2C9 variants found in the Chinese population on losartan metabolism in vitro. Xenobiotica. 2014 Mar;44(3):270–275.
   PubMed Web of Science ®Google Scholar
• Sica DA, Gehr TWB, Ghosh S. Clinical pharmacokinetics of Losartan. Clin Pharmacokinet. 2005;44(8):797–814.
   PubMed Web of Science ®Google Scholar
• Wang Z, Wang L, Xu RA, et al. Role of cytochrome P450 2D6 genetic polymorphism in carvedilol hydroxylation in vitro. Drug Des Devel Ther. 2016;10:1909–1916.
   PubMed Web of Science ®Google Scholar
• Pan PP, Weng QH, Zhou CJ, et al. The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro. Eur J Drug Metab Pharmacokine. 2016 Feb;41(1):79–86.
   PubMed Web of Science ®Google Scholar
• Yue TL, McKenna PJ, Gu JL, et al. Carvedilol, a new vasodilating beta adrenoceptor blocker antihypertensive drug, protects endothelial cells from damage initiated by xanthine-xanthine oxidase and neutrophils. Cardiovasc Res. 1994 Mar;28(3):400–406.
   PubMed Web of Science ®Google Scholar
• Oldham HG, Clarke SE. In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilol. Drug Metab Dispos. 1997 Aug;25(8):970–977.
   PubMed Web of Science ®Google Scholar
• Zhou SF, Zhou ZW, Yang LP, et al. Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480–3675.
   PubMed Web of Science ®Google Scholar
• Nardotto GHB, Lanchote VL, Coelho EB, et al. Population pharmacokinetics of carvedilol enantiomers and their metabolites in healthy subjects and type-2 diabetes patients. Eur J Pharm Sci. 2017 Nov 15;109:S108–S115.
   Web of Science ®Google Scholar
• Oldham HG, Clarke SE. In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilol. Drug Metab Disp Biol Fate Chem. 1997;25(8):970.
   PubMed Web of Science ®Google Scholar
• Zhou XY, Hu XX, Li MF, et al. Functional characterization of CYP2C19 variants in nebivolol 4-hydroxlation in vitro. Drug Test Anal. 2018 May;10(5):807–813.
   PubMed Web of Science ®Google Scholar
• Hu XX, Lan T, Dai DP, et al. Evaluation of 24 CYP2D6 variants on the metabolism of nebivolol in vitro. Drug Metab Dispos. 2016 Nov;44(11):1828–1831.
   PubMed Web of Science ®Google Scholar
• Guo LF, Wang SM, Wan ZR, et al. Influence of CYP2D6*5 and *10 polymorphism on the pharmacokinetics of nebivolol in healthy Chinese subjects. J Clin Pharm Ther. 2020 Aug;45(4):632–637.
   PubMed Web of Science ®Google Scholar
• Gielen W, Cleophas TJ, Agrawal R. Nebivolol: a review of its clinical and pharmacological characteristics. Int J Clin Pharmacol Ther. 2006 Aug;44(8):344–357.
   PubMed Web of Science ®Google Scholar
• Jin TB, Zhang XY, Geng TT, et al. Genotype-phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy. Mol Med Rep. 2016 Mar;13(3):2117–2123.
   PubMed Web of Science ®Google Scholar
• Ding YP, Xu DC, Zhang XY, et al. Genetic polymorphisms and phenotypic analysis of drug-metabolizing enzyme CYP2C19 in a Li Chinese population. Int J Clin Exp Patho. 2015;8(10):13201–13208.
   PubMed Web of Science ®Google Scholar
• Liang BQ, Zhan YY, Huang XX, et al. Effect of 22 Novel Cytochrome P450 2D6 (CYP2D6) variants found in the chinese population on hemangeol metabolism in vitro. Eur J Drug Metab Pharmacokine. 2016 Dec;41(6):759–765.
   PubMed Web of Science ®Google Scholar
• Yoshimoto K, Echizen H, Chiba K, et al. Identification of human CYP isoforms involved in the metabolism of propranolol enantiomers–N-desisopropylation is mediated mainly by CYP1A2. Br J Clin Pharmacol. 1995 Apr;39(4):421–431.
   PubMed Web of Science ®Google Scholar
• Masubuchi Y, Hosokawa S, Horie T, et al. Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. The role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase. Drug Metab Dispos. 1994 Nov-Dec;22(6):909–915.
   PubMed Web of Science ®Google Scholar
• Lai ML, Su-Lan Wang MS, Lai MD, et al. Propranolol disposition in Chinese subjects of different CYP2D6 genotypes. Clin Pharmacol Ther. 1995;58(3):264–268.
   PubMed Web of Science ®Google Scholar
• Li XY, Hu XX, Yang F, et al. Effects of 24 CYP2D6 variants found in Chinese population on the metabolism of clonidine in vitro. Chem Biol Interact. 2019 Nov 1;313:108840.
   Web of Science ®Google Scholar
• Chen MC, Zhang YT, Pan PP, et al. Effects of Cytochrome P450 2C9 Polymorphism on Bosentan Metabolism. Drug Metab Dispos. 2014 Nov;42(11):1820–1825.
   PubMed Web of Science ®Google Scholar
• Dhillon S, Keating GM. Bosentan. Am J Cardiovasc Drugs. 2009;9(5):331–350.
   PubMedGoogle Scholar
• Dingemanse J, Appel-Dingemanse S. Integrated pharmacokinetics and pharmacodynamics in drug development. Clin Pharmacokinet. 2007;46(9):713–737.
   PubMed Web of Science ®Google Scholar
• Feng S, He X. Mechanism-based Inhibition of CYP450: an Indicator of Drug-induced Hepatotoxicity. Curr Drug Metab. 2013 Nov;14(9):921–945.
   PubMed Web of Science ®Google Scholar
• Gaedigk A, Simon SD, Pearce RE, et al. The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin Pharmacol Ther. 2008 Feb;83(2):234–242.
   PubMed Web of Science ®Google Scholar