Потенциальные взаимодействия лекарственных средств и чеснока

Прием лекарственных средств (ЛС) потенциально ассоциирован с риском развития нежелательных реакций (НР), особенно часто со стороны центральной нервной системы, желудочно-кишечного тракта и сердечно-сосудистой системы. При этом зачастую врачи не обладают достаточной информацией, что увеличивать риски развития НР может взаимодействие ЛС с некоторыми продуктами питания, в частности с чесноком. С начала XX века и до настоящего времени чеснок был предметом многих химических исследований, которые выявили некоторые различия в химическом составе исследуемого препарата (свежий или хранящийся чеснок). Наиболее важные химические ингредиенты, содержащиеся в чесноке, делятся на две группы: серосодержащие (аллицин [диаллилтиосульфинат], аллилметансульфинат, аллиин [сульфоксид S-аллил-L-цистеина], диаллил дисульфид [diallyl disulfide, DADS], S-аллил цистеин, аллилметил трисульфид, диаллил трисульфид [diallyl trisulfide, DATS], аллил метил трисульфид, аллилметил дисульфид, диаллил тетрасульфид, аллилметилтетрасульфид, диметил трисульфид, диаллил сульфид, 2-винил-4-H1,3-дитиин, 3-винил-4-H1,2-дитиин) и несодержащие серу соединения. Большинство фармакологических эффектов чеснока обусловлено соединениями серы, в частности аллицином. В экспериментах на животных, in vitro и клинических исследованиях было показано, что чеснок может вступать в фармакокинетические и фармакодинамические взаимодействия с различными ЛС. Например, экстракт чеснока показал способность ингибировать метаболическую активность CYP2C9*1, 2C19, 3A4, 3A5, 3A7, но не CYP2D6. Также было показано, что чеснок может влиять на функцию тромбоцитов и свертываемость крови, что приводит к увеличению риска кровотечения, что особенно актуально в случае одновременного его употребления с антиагрегантами и (или) антикоагулянтами. В данной статье представлен обзор открытых литературных источников, посвященных рискам и пользе одновременного применения ЛС и продуктов, содержащих чеснок.

1. Сычев Д.А., Остроумова О.Д., Кочетков А.И., Переверзев А.П., Остроумова Т.М., Клепикова М.В., Аляутдинова И.А., Эбзеева Е.Ю. Лекарственно-индуцированные заболевания: эпидемиология и актуальность проблемы. Фарматека. 2020. Т. 27. № 5. С. 77–84.

2. Angamo M.T., Chalmers L., Curtain C. M., Bereznicki L. R. Adverse-Drug-Reaction-Related Hospitalisations in Developed and Developing Countries: A Review of Prevalence and Contributing Factors. Drug Saf. 2016; 39 (9): 847–57. https://doi.org/10.1007/s40264–016–0444–7

3. Hakkarainen K.M., Gyllensten H., Jonsson A.K., et al. Prevalence, nature and potential preventability of adverse drug events: a population-based medical record study of 4970 adults. Br J Clin Pharmacol. 2014; 78 (1): 170–83. https://doi.org/10.1111/bcp.12314

4. Tisdale JE, Miller DA. Drug Induced Diseases: Prevention, Detection, and Management. 3rd Ed. Bethesda, Md.: American Society of Health-System Pharmacists; 2018; 1399 рр.

5. Koziolek M, Alcaro S, Augustijns P, Basit AW, Grimm M, Hens B, Hoad CL, Jedamzik P, Madla CM, Maliepaard M, Marciani L, Maruca A, Parrott N, Pávek P, Porter CJH, Reppas C, van Riet-Nales D, Rubbens J, Statelova M, Trevaskis NL, Valentová K, Vertzoni M, Čepo DV, Corsetti M. The mechanisms of pharmacokinetic food-drug interactions – A perspective from the UNGAP group. Eur J Pharm Sci. 2019 Jun 15; 134: 31–59. DOI: 10.1016/j.ejps.2019.04.003.

6. O’Shea JP, Holm R, O’Driscoll CM, Griffin BT. Food for thought: formulating away the food effect – a PEARRL review. J Pharm Pharmacol. 2019 Apr; 71 (4): 510–535. DOI: 10.1111/jphp.12957.

7. Aviello G, Abenavoli L, Borrelli F, Capasso R, Izzo AA, Lembo F, Romano B, Capasso F. Garlic: empiricism or science? Nat Prod Commun. 2009 Dec; 4 (12): 1785–96.

8. Amagase H, Petesch BL, Matsuura H, Kasuga S, Itakura Y. Intake of garlic and its bioactive components. J Nutr. 2001 Mar; 131 (3s): 955S-62S. DOI: 10.1093/jn/131.3.955S.

9. Nagini S. Cancer chemoprevention by garlic and its organosulfur compounds-panacea or promise? Anticancer Agents Med Chem. 2008 Apr; 8 (3): 313–21. DOI: 10.2174/187152008783961879.

10. Seki T, Hosono T, Hosono-Fukao T, Inada K, Tanaka R, Ogihara J, Ariga T. Anticancer effects of diallyl trisulfide derived from garlic. Asia Pac J Clin Nutr. 2008; 17 Suppl 1: 249–52.

11. Raghu R, Lu KH, Sheen LY. Recent Research Progress on Garlic (dà suàn) as a Potential Anticarcinogenic Agent Against Major Digestive Cancers. J Tradit Complement Med. 2012 Jul; 2 (3): 192–201. DOI: 10.1016/s2225–4110(16)30099–2.

12. Münchberg U, Anwar A, Mecklenburg S, Jacob C. Polysulfides as biologically active ingredients of garlic. Org Biomol Chem. 2007 May 21; 5 (10): 1505–18. DOI: 10.1039/b703832a.

13. Block E. The chemistry of garlic and onions. Sci Am. 1985 Mar; 252 (3): 114–9. DOI: 10.1038/scientificamerican0385–114.

14. Omar SH, Al-Wabel NA. Organosulfur compounds and possible mechanism of garlic in cancer. Saudi Pharm J. 2010; 18 (1): 51–58. DOI: 10.1016/j.jsps.2009.12.007.

15. Nasir A Siddiqui, Ramzi A Mothana and Perwez Alam. Quantitative determination of alliin in dried garlic cloves and products by high-performance thin-layer chromatography. Tropical Journal of Pharmaceutical Research August 2016; 15 (8): 1759–1765. http://dx.doi.org/10.4314/tjpr.v15i8.23

16. Kishimoto R, Ueda M, Yoshinaga H, Goda K, Park SS. Combined effects of ethanol and garlic on hepatic ethanol metabolism in mice. J Nutr Sci Vitaminol (Tokyo). 1999 Jun; 45 (3): 275–86. DOI: 10.3177/jnsv.45.275.

17. Foster BC, Foster MS, Vandenhoek S, Krantis A, Budzinski JW, Arnason JT, Gallicano KD, Choudri S. An in vitro evaluation of human cytochrome P450 3A4 and P-glycoprotein inhibition by garlic. J Pharm Pharm Sci. 2001 May-Aug; 4 (2): 176–84.

18. Jin L, Baillie TA. Metabolism of the chemoprotective agent diallyl sulfide to glutathione conjugates in rats. Chem Res Toxicol. 1997 Mar; 10 (3): 318–27. DOI: 10.1021/tx9601768.

19. Teyssier C, Guenot L, Suschetet M, Siess MH. Metabolism of diallyl disulfide by human liver microsomal cytochromes P-450 and flavin-containing monooxygenases. Drug Metab Dispos. 1999 Jul; 27 (7): 835–41.

20. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John’s wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging. 2005; 22 (6): 525–39. DOI: 10.2165/00002512–200522060–00006.

21. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther. 2002 Sep; 72 (3): 276–87. DOI: 10.1067/mcp.2002.126913.

22. Borrelli F, Capasso R, Izzo AA. Garlic (Allium sativum L.): adverse effects and drug interactions in humans. Mol Nutr Food Res. 2007 Nov; 51 (11): 1386–97. DOI: 10.1002/mnfr.200700072.

23. Piscitelli SC, Burstein AH, Welden N, Gallicano KD, Falloon J. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis. 2002 Jan 15; 34 (2): 234–8. DOI: 10.1086/324351.

24. Gallicano K, Foster B, Choudhri S. Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2003; 55 (2): 199–202. DOI: 10.1046/j.1365–2125.2003.01736.x.

25. Laroche M, Choudhuri S, Gallicano K, Foster B. Severe gastrointestinal toxicity with concomitant ingestion of ritonavir and garlic. The Canadian Journal of Infectious Diseases. 1998; 9: 471.

26. Heck AM, Dewitt BA, Lukes AL. Potential Interactions Between Alternative Therapies and Warfarin. American Journal of Health-System Pharmacy. 2000; 57: 13.

27. Avula PR, Asdaq SM, Asad M. Effect of aged garlic extract and s-allyl cysteine and their interaction with atenolol during isoproterenol induced myocardial toxicity in rats. Indian J Pharmacol. 2014 Jan-Feb; 46 (1): 94–9. DOI: 10.4103/0253–7613.125185.

28. Wojcikowski K, Myers S, Brooks L. Effects of garlic oil on platelet aggregation: a double-blind placebo-controlled crossover study. Platelets. 2007 Feb; 18 (1): 29–34. DOI: 10.1080/09537100600800636.

29. Asdaq SMB, Inamdar MN. Interaction of propranolol with garlic in Biochemical and Histological Changes in rat. Iranian Journal of Pharmaceutical Research. 2009; 8 (3): 201–7.

30. Adhikari A, Indu R, Sur TK, Banerjee D, Das AK. Is Garlic a Safe Remedy: An Overlook Herb Drug Interaction? American Journal of Phytomedicine and Clinical Therapeutics. 2015; 3: 622–32.

31. Wang Y, Zou M, Zhao N, Ren J, Zhou H, Cheng G. Effect of diallyl trisulfide on the pharmacokinetics of nifedipine in rats. J Food Sci. 2011; 76: 30–4.

32. Asdaq SM, Inamdar MN. Potential of garlic and its active constituent, S-allyl cysteine, as antihypertensive and cardioprotective in presence of captopril. Phytomedicine. 2010 Nov; 17 (13): 1016–26. DOI: 10.1016/j.phymed.2010.07.012.

33. Endo A. The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res. 1992 Nov; 33 (11): 1569–82.

34. Reddy GD, Reddy AG, Rao GS, Haritha C, Jyothi K. Interaction study on garlic and atorvastatin with reference to nephrotoxicity in dyslipidaemic rats. Toxicol Int. 2010 Jul; 17 (2): 90–3. DOI: 10.4103/0971–6580.72678.

35. Piscitelli SC, Burstein AH, Welden N, Gallicano KD, Falloon J. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis. 2002 Jan 15; 34 (2): 234–8. DOI: 10.1086/324351.

36. Piscitelli SC, Burstein AH, Welden N, Gallicano KD, Falloon J. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis. 2002 Jan 15; 34 (2): 234–8. DOI: 10.1086/324351.

37. Kraus LA, Samuel SK, Schmid SM, Dykes DJ, Waud WR, Bissery MC. The mechanism of action of docetaxel (Taxotere) in xenograft models is not limited to bcl-2 phosphorylation. Invest New Drugs. 2003 Aug; 2 1(3): 259–68. DOI: 10.1023/a:1025436307913.

38. Frenkel M, Gupta A. Nutritional Supplements and Docetaxel: Avoid or Combine? Journal of the Society for Integrative Oncology. 2010; 8: 120–25.

39. Luzi L, Pozza G. Glibenclamide: an old drug with a novel mechanism of action? Acta Diabetol. 1997 Dec; 34 (4): 239–44. DOI: 10.1007/s005920050081.

40. Poonam T, Prakash GP, Kumar LV. Influence of Allium sativum extract on the hypoglycemic activity of glibenclamide: an approach to possible herb-drug interaction. Drug Metabol Drug Interact. 2013; 28 (4): 225–30. DOI: 10.1515/dmdi-2013–0031.

41. Timmins GS, Deretic V. Mechanisms of action of isoniazid. Mol Microbiol. 2006 Dec; 62 (5): 1220–7. DOI: 10.1111/j.1365–2958.2006.05467.x.

42. Dhamija P, Malhotra S, Pandhi P. Effect of oral administration of crude aqueous extract of garlic on pharmacokinetic parameters of isoniazid and rifampicin in rabbits. Pharmacology. 2006; 77 (2): 100–4. DOI: 10.1159/000093285.

43. Graham GG, Scott KF. Mechanism of action of paracetamol. Am J Ther. 2005 Jan-Feb; 12 (1): 46–55. DOI: 10.1097/00045391–200501000–00008.

44. Izzo AA. Herb-drug interactions: an overview of the clinical evidence. Fundam Clin Pharmacol. 2005 Feb; 19 (1): 1–16. DOI: 10.1111/j.1472–8206.2004.00301.x.

45. Matsuda S, Koyasu S. Mechanisms of action of cyclosporine. Immunopharmacology. 2000 May; 47 (2–3): 119–25. DOI: 10.1016/s0162–3109(00)00192–2.

46. Emidicineshealth. Garlic medicine health. Available at http://www.emedicinehealth.com/garlic-page3/vitamins-supplements.htm (accessed: 10.08.2021).

47. Liu YC, Lo YK, Wu SN. Stimulatory effects of chlorzoxazone, a centrally acting muscle relaxant, on large conductance calcium-activated potassium channels in pituitary GH3 cells. Brain Res. 2003 Jan 3; 959 (1): 86–97. DOI: 10.1016/s0006–8993(02)03730–7.

48. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John’s wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging. 2005; 22 (6): 525–39. DOI: 10.2165/00002512–200522060–00006.

49. Berginc K, Kristl A. The effect of garlic supplements and phytochemicals on the ADMET properties of drugs. Expert Opin Drug Metab Toxicol. 2012 Mar; 8 (3): 295–310. DOI: 10.1517/17425255.2012.659662.

50. Macan H, Uykimpang R, Alconcel M, Takasu J, Razon R, Amagase H, Niihara Y. Aged garlic extract may be safe for patients on warfarin therapy. J Nutr. 2006 Mar; 136 (3 Suppl): 793S-795S. DOI: 10.1093/jn/136.3.793S.

51. Mohammed Abdul MI, Jiang X, Williams KM, Day RO, Roufogalis BD, Liauw WS, Xu H, McLachlan AJ. Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects. Br J Pharmacol. 2008 Aug; 154 (8): 1691–700. DOI: 10.1038/bjp.2008.210.

52. Ried K, Frank OR, Stocks NP, Fakler P, Sullivan T. Effect of garlic on blood pressure: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2008 Jun 16; 8: 13. DOI: 10.1186/1471–2261–8–13.