Preview

Rational Pharmacotherapy in Cardiology

Advanced search

THE ROLE OF P-GLYCOPROTEIN IN RATIONAL PHARMACOTHERAPY IN CARDIOLOGY

https://doi.org/10.20996/1819-6446-2013-9-6-701-707

Full Text:

Abstract

On the basis of the analysis of published data the role of P-glycoprotein, carrier protein, in rational pharmacotherapy in cardiology was shown on the example of its substrates – digoxin, antiplatelet agents and anticoagulants. Determination of C3435T polymorphism of multidrug resistance gene (MDR1), encoding P-glycoprotein, in pharmacotherapy with digoxin, antiplatelet drugs (clopidogrel tikagrelol, prasugrel) and anticoagulants (dabigatran etexilate, rivaroxaban, edoxaban) is not feasible in routine practice. Drug in- teractions have clinical implications for the efficacy and safety of pharmacotherapy in coadministration of these drugs with P-glycoprotein substrates, inducers and inhibitors.

About the Authors

A. V. Shulkin
Ryazan State Ivan Petrovich Pavlov Medical University, Ryazan
Russian Federation


E. N. Yakusheva
Ryazan State Ivan Petrovich Pavlov Medical University, Ryazan
Russian Federation


N. M. Popova
Ryazan State Ivan Petrovich Pavlov Medical University, Ryazan
Russian Federation


References

1. Li Y, Yuan H, Yang K, et al. The structure and function of P-glycoprotein. Curr Med Chem 2010;17(8):786-800.

2. Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell nutans. Biochem Biophis Acta 1976;455(1):155-62.

3. Sharom FJ. The P-glycoprotein multidrug transporter. Essays Biochem 2011;50:161-78.

4. Lee CY, Lai TY, Wu YM, et al. Gene Expression of P-glycoprotein and Cytochrome P450 3A4 in Peripheral Blood Mononuclear Cells and Correlation With Expression in Liver. Transplant Proc 2010;42(3):834-6.

5. Choi YH, Yu AM. ABC transporters in Multidrug Resistance and Pharmacokinetics, and Strategies for Drug Development. Curr Pharm Des 2013. [Epub ahead of print].

6. Hudachek SF, Gustafson DL. Incorporation of ABCB1-mediated transport into a physiologically-based pharmacokinetic model of docetaxel in mice. J Pharmacokinet Pharmacodyn 2013;40(4):437-49.

7. Callen DF, Baker E, Simmers RN, et al. Localization of the human multiple drug resistance gene, MDR1, to 7q21.1. Hum Genet 1987;77:142-4.

8. Database of single nucleotide polymorphisms (SNPs) NCBI. (www.ncbi.nlm.nih.gov/SNP/ GeneGt.cgi?geneID=5243).

9. Zhou SF. Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiot 2008;8(7-8):802-32.

10. Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Nat Acad Sci 2000;97(7):3473-8.

11. Kukes VG, Grachev SV, Sychev DA, Ramenskaya GV. Metabolism of drugs. Scientific bases of personal medicine: A guide for medical practitiones. Moscow: GEOTAR-Media; 2008. Russian (Кукес В.Г, Грачев С.В, Сычев Д.А., Раменская Г.В. Метаболизм лекарственных средств. Научные основы персонализованной медицины: руководство для врачей. М.: ГЭОТАР-Медиа; 2008.)

12. Yakusheva EN, Chernyh IV, Birukova AS. The influence of finasteride on the function activity of P-glycoprotein. Rossiyskiy Mediko-Biologicheskiy Vestnik Imeni Akademika I.P. Pavlova 2012;(4):46-50. Russian (Якушева Е.Н., Черных И.В., Бирюкова А.С. Влияние финастерида на функциональную активность гликопротеина-P в эксперименте. Российский Медико-Биологический Вестник Имени Академика И.П. Павлова 2012;(4):46-50).

13. Yakusheva EN, Chernyh IV. Characteristic of P-glycoprotein as transporter of drugs. Rossiyskiy Mediko-Biologicheskiy Vestnik Imeni Akademika I.P. Pavlova 2011;(3):142-8. Russian (Якушева Е.Н., Черных И.В. Характеристика гликопротеина-P как белка-транспортера лекарственных веществ. Российский Медико-Биологический Вестник Имени Академика И.П. Павлова 2011;(3):142-8).

14. Biriukova AS, Yakusheva EN, Schulkin AV, Nikiforova LV. The influence of L—thyroxine on the function аctivity of P-glycoprotein. Rossiyskiy Mediko-Biologicheskiy Vestnik Imeni Akademika I.P. Pavlova 2011;(4):49-53. Russian (Бирюкова А.С., Якушева Е.Н., Щулькин А.В., Никифорова Л.В. Влияние тироксина на функциональную активность гликопротеина-Р в эксперименте. Российский Медико-Биологический Вестник Имени Академика И.П. Павлова 2011;(4):49-53).

15. Wessler DJ, Grip LT, Mendell J, Giugliano RP. The P-Glycoprotein Transport System and Cardiovascular Drugs. JACC 2013;61(25):2495-502.

16. U.S. Food and Drug Administration, Center for Drug Evaluationand Research. Guidance for industry: drug interaction studiesdstudy design, data analysis, implications for dosing, and labeling recommendations. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulato- ryInformation/Guidances/ucm292362.pdf.

17. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525-33.

18. Hoffmeyer S., Burk O., von Richter O. et al. Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Nat Acad Sci 2000;97(7):3473-8.

19. Balram C., Huihua Li, Machin D. et al. Meta-analysis of the influence of MDR1 C3435T polymorphism on digoxin pharmacokinetics and MDR1 gene expression. Br J Clin Pharm 2005; 60(2):159-71.

20. Johne A, Kopke K, Gerloff T, et al. Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene. Clin Pharmacol Ther 2002;72:584-94.

21. Stephens RH, O'Neill CA, Warhurst A, et al. Kinetic profiling of P-glycoprotein-mediated drug efflux in rat and human intestinal epithelia. J Pharmacol Exp Ther 2001;296:584-91.

22. Kurzawski M, Bartnicka L, Florczak M, et al. Impact of ABCB1 (MDR1) gene polymorphism and P-glycoprotein inhibitors on digoxin serum concentration in congestive heart failure patients. Pharmacol Rep 2007;59(1):107-11.

23. Greiner B, Eichelbaum M, Fritz P, et al. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J Clin Invest 1999;104(2):147-53.

24. Juurlink DN, Mamdani M, Kopp A. Drug-Drug Interactions Among Elderly Patients Hospitalized for Drug Toxicity. JAMA 2003;289(13):1652-8.

25. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation. Eur Heart J 2008;29(23):2909-45.

26. Guidelines on the management of stable angina pectoris: executive summary. Eur Heart J 2006;27(11):1341-81.

27. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354-62.

28. Sugunaraj JP, Palaniswamy C, Selvaraj DR, et al. Clopidogrel resistance. Am J Ther 2010;17:210-5.

29. Snoep JD, Hovens MM, Eikenboom JC, et al. Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis. Am Heart J 2007;154:221-31.

30. Taubert D, von Beckerath N, Grimberg G, et al. Impact of P-glycoprotein on clopidogrel absorption. Clin Pharmacol Ther 2006;80(5):486-501.

31. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009;360:363-75.

32. Su J, Xu J, Li X, et al. ABCB1 C3435T Polymorphism and Response to Clopidogrel Treatment in Coronary Artery Disease (CAD) Patients: A Meta-Analysis. PLoS ONE 2012;7(10): e46366.

33. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2011;32(23):2999-3054.

34. Kim IS, Jeong YH, Park Y, et al. Interaction analysis between genetic polymorphisms and pharmacodynamic effect in patients treated with adjunctive cilostazol to dual antiplatelet therapy: results of the ACCEL-TRIPLE (Accelerated Platelet Inhibition by Triple Antiplatelet Therapy According to Gene Poly- morphism) study. Br J Clin Pharmacol 2012;73(4):629-40.

35. Jaitner J, Morath T, Byrne RA, et al. No association of ABCB1 C3435T genotype with clopidogrel response or risk of stent thrombosis in patients undergoing coronary stenting. Circ Cardiovasc Interv 2012;5(1):82-8.

36. Luo M, Li J, Xu X, Sun X, Sheng W. ABCB1 C3435T polymorphism and risk of adverse clinical events in clopidogrel treated patients: a meta-analysis. Thromb Res 2012;129(6):754-9

37. Teng R, Butler K. A pharmacokinetic interaction study of ticagrelor and digoxin in healthy volunteers. Eur J Clin Pharmacol 2013;69(10):1801-8.

38. Wallentin L, James S, Storey RF, et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet 2010;376:1320-8.

39. Small DS, Farid NA, Payne CD, et al. Atorvastatin coadministration may increase digoxin concentrations by inhibition of intestinal P-glycoprotein-mediated secretion. J Clin Pharmacol 2000;40:91-8.

40. Eisert WG, Hauel N, Stangier J, et al. Dabigatran: An Oral Novel Potent Reversible Nonpeptide Inhibitor of Thrombin. ATVB 2010;30:1885-9.

41. Stangier J, Clemens A. Pharmacology, pharmacokinetics and pharmacodynamics of dabigatran etexilate an oral direct thrombin inhibitor. Clin Appl Thromb/Hemost 2009;15:9-16.

42. Pare G, Eriksson N, Lehr T, et al. Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding. Circulation 2013;127:1404-12.

43. Pradaxa (dabigatran etexilate). Prescribing information. Available at: http://bidocs.boehringer-in-gelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf

44. Walenga JM, Adiguzel C. Drug and dietary interactions of the new and emerging oral anticoagulants. Int J Clin Pract 2010;64:956-67.

45. Härtter S, Sennewald R, Nehmiz G, et al. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects. Br J Clin Pharmacol 2013;75(4):1053-62.

46. Kawabata M, Yokoyama Y, Sasano T, et al. Bleeding events and activated partial thromboplastin time with dabigatran in clinical practice. J Cardiol 2013;62(2):121-6.

47. Douketis JD. Pharmacologic properties of the new oral anticoagulants: a clinician-oriented review with a focus on perioperative management. Curr Pharm Des 2010;16:3436-41

48. Kubitza D, Becka M, Roth A, Mueck W. Absence of clinically relevant interactions between rivaroxaban - an oral, direct Factor Xa inhibitor--and digoxin or atorvastatin in healthy subjects. J Int Med Res 2012;40(5):1688-707.

49. Xarelto® (rivaroxaban). Summary of product characteristics. Available at: http://www.xarelto.com/en/in-formation-on-xarelto/summary-of-product-characteristics/.

50. Mendell J, Noveck RJ, Shi M. Pharmacokinetics of the direct factor Xa inhibitor edoxaban and digoxinadministered alone and in combination. J Cardiovasc Pharmacol 2012;60(4):335-41

51. Mendell J, Zahir H, Matsushima N, et al. Drug-Drug Interaction Studies of Cardiovascular Drugs Involving P-Glycoprotein, an Efflux Transporter, on the Pharmacokinetics of Edoxaban, an Oral Factor Xa Inhibitor. Am J Cardiovasc Drugs 2013;13(5):331-42

52. Ruff CT, Giugliano RP, Antman EM, et al. Evaluation of the novel factor Xa inhibitor edoxaban com- pared with warfarin in patients with atrial fibrillation: design and rationale for the Effective AnticoagulationWith Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis.In Myocardial Infarction Study 48 (ENGAGE AF-TIMI 48). Am Heart J 2010;160:635-41.

53. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651.


Review

For citation:


Shulkin A.V., Yakusheva E.N., Popova N.M. THE ROLE OF P-GLYCOPROTEIN IN RATIONAL PHARMACOTHERAPY IN CARDIOLOGY. Rational Pharmacotherapy in Cardiology. 2013;9(6):701-707. (In Russ.) https://doi.org/10.20996/1819-6446-2013-9-6-701-707

Views: 710


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)