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Cytochrome P-450 3A4 system in patients with acute myocardial infarction

Abstract

Aim. To investigate CYP 3A4 system functioning and its clinico-laboratory correlations in acute myocardial infarction (AMI).

Material and methods. The study included 50 patients hospitalized in the first 24 hours of AMI with ST segment elevation (STE-AMI). Monoethylglycinexylidide (MEGX) test was performed at the hospital admission, at Day 4-5 and Day 14.

Results. Baseline MEGX level was significantly higher in non-complicated AMI group (132,1+16,85 ng/ml) than in patients with heart failure (HF) symptoms (31,9+2,02 ng/ml; p<0,001) or healthy volunteers (63,6+14,01 ng/ ml; p<0,001). Phenobarbital administration significantly enhanced CYP 3A4 activity in both AMI groups.

Conclusion. In AMI, CYP 3A4 system activity was suppressed among patients with acute HF symptoms. This could be explained by ischemic and congestive liver disturbances. In STE-AMI, pharmacological CYP 3A4 stimulation is possible.

About the Authors

A. G. Vladimirov
ГУЗ Госпиталь для ветеранов войн №3
Russian Federation


V. G. Kukes
Clinical Pharmacology Institute, Research Center for Medical Substances Expertise
Russian Federation


D. A. Andreev
I.M. Sechenov Moscow Medical Academy. Moscow
Russian Federation


References

1. Применение MEGX-теста для оценки активности изо-фермента цитохрома 3-450 ЗА4. Методические рекомендации. Москва 2004.

2. Метаболизм лекарственных препаратов. Под ред. акад. РАМН проф. В.Г.Кукеса. Москва "Палея-М" 2004.

3. Клиническая фармакология под ред. акад. РАМН, проф. Кукеса В.Г. Москва "ГЭОТАР-МЕД" 2004.

4. Braunwald's Heart disease: A textbook of Cardiovascular Medicine, 7th edition, Elsevier Saunders. Philadelphia 2006.

5. Bailey D.G., Dresser G.K. Interactions between grapefruit juice and cardiovascular drugs. Am J Cardiovasc Drugs 2004; 4: 281-97.

6. Giesen P.L., Peltenburg H.G., de Zwaan C., et al. Greater than expected alanine aminotransferase activities in plasma and in hearts of patients with acute myocardial infarction. Clin Chem 1989; 35(2): 279-83.

7. Гузеева В.А. Патология печени при инфаркте миокарда. Кардиология 1977; 17(1): 119-23.

8. Halkin H, Meffin P, Melmon KL, Rowland M. Influence of congestive heart failure on blood vessels of lidocaine and its active monodeethylated metabolite. Clin Pharmacol Ther 1975; 17: 669-76.

9. Hayashi M. Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post -infarction left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. J Cardiol 2004; 43: 88-91.

10. Igonin AA, Armstrong VW, Shipkova M, et al. The monoethylexilidide (MEGX) test as a marker of hepatic dysfunction in septic patients with pneumonia. Clin Chem Lab Med 2000; 38: 1125-8.

11. Маха J.L., Melton L.B., Ogu C.C., et al. Rhabdomyolysis after concomitant use of cyclosporine, simvastatin,gemfibrosil and intraconazole. Ann Pharmacother 2002; 36: 820-3.

12. Narang P.K.,Grouthamel W.G., Carliner N.H., Fisher M.L. Lidocaine and its active metabolites. Clin Pharmacol Ther 1978; 24: 654-62.

13. Neubauer H., Mugge A. Thienopyridines aand statins: assessing a potential drug-drug interaction. Curr Pharm Des 2006; 12: 1271-80.

14. Oellerich M., Armstrong V.W. The MEGX test: a tool for the real-time assessment of hepatic function. Ther Drug Monit 2001; 23: 81-92.

15. Oostenbrock R.J., Willems G.M., Boumans M.L., et al. Luver damage as a potential source of error in the estimation of myocardial infarct size from plasma creatine kinase activity. Cardiovasc Res 1985; 19(2): 113-9.

16. Pitt B., Remme W., Zannad F., et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348(14): 1309-21.

17. Plant N.J., Gibson G.G. Evaluation of the toxicological relevance of CYP3A4 induction. Curr Opin Drug Discov Devel 2003; 6: 50-6.

18. Ucar M., Mjorndat T., Dahlqvist R. HMG-CoA reductase inhibitors and myotoxicity. Drug Saf 2000; 22: 441-57.

19. Willims D., Feely J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmakokinet 2002;41:343-70.

20. Yamreudeewong W., DeBisschop M., Martin L.G., Lower D.L. Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Saf 2003; 26: 421-38.


Review

For citations:


Vladimirov A.G., Kukes V.G., Andreev D.A. Cytochrome P-450 3A4 system in patients with acute myocardial infarction. Cardiovascular Therapy and Prevention. 2008;7(4):35-40. (In Russ.)

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ISSN 1728-8800 (Print)
ISSN 2619-0125 (Online)