Расширенный поиск

Полиморфизм генов системы детоксикации ксенобиотиков и его роль в биотрансформации внутривенных анестетиков

Полный текст:


Despite of wide arsenal of drugs for narcosis, existing now, quite often the anaesthesiologist is faced with the problem of optimum diagram of anaesthesia. Evaluation age, social, emotional characteristics of patient is often not enough. That is why studying SNP-polymorphisms and their influence on a metabolism of anaesthetics, probably will allow to optimize the concept of «individual approach» in anaesthesiologia. A substantial part of the individual variability of person response to drugs is related with single nucleotides polymorphisms. Drugs that are used in general anesthesia undergo polymorphic metabolism. Among these, CYP2B6, CYP3A4 and CYP2C9 play a relevant role in the metabolism of ketamine. The enzymes involved in the metabolism of thiopental are still unknown. Propofol is metabolized mainly by glucuronidation by uridine diphosphate-glucuronosyltransferases (UGTs) and by hydroxylation by CYP2B6 and CYP2C enzymes. The enzymes SULT1A1 and NQO1 participate in later steps in propofol metabolism. CYP3A4, CYP3A5, CYP2B6, CYP2C19 play significant role in later steps in propofol metabolism. CYP3A4, CYP3A5, CYP2B6, CYP2C19 play significant role in the metabolism of benzodiazepines. The present review analyses the importance of enzymes in the metabolism of anaesthetics.

Об авторах

О. А. Махарин
Ростовский государственный медицинский университет, Ростов-на-Дону

Ю. С. Макляков
Ростовский государственный медицинский университет, Ростов-на-Дону

В. М. Женило
Ростовский государственный медицинский университет, Ростов-на-Дону

Список литературы

1. Волчков В.А., Игнатов Ю.Д., Страшнов В.И. Болевые синдромы в анестезиологии и реаниматологии – М.: МЕДпресс-информ. 2006.

2. Каркищенко Н.Н. Основы биомоделирования – М.: Межакадемическое издательство ВПК. 2004.

3. Кукес В.Г., Грачев С.В., Сычев Д.А., Раменская Г.В. Метаболизм лекарственных средств, научные основы персонализированной медицины М.: ГЕ- ОТАР-Медиа. 2008.

4. Сарвилина И.В., Каркищенко В.Н., Горшкова Ю.В. Мир биологии и медицины. Междиссиплинарные исследования в медицине – М.: ТЕХНОСФЕ- РА. 2007.

5. Симон В.А. Цитохром Р-450 и взаимодействие лекарственных веществ / Материалы VII Российской конференции «Гепатология сегодня». 2002.

6. Сычев Д.А. Клиническая фармакогенетика. Клиническая фармакология / под ред. акад. РАМН, проф. Кукеса В.Г. – М.: ГЕОТАР-Медиа. 2004.

7. Carlos Isaza; Julieta Henao Jose; H Isaza Martinez, Juan C. Sepulveda Arias, Leonardo Beltran. Phenotype-genotype analysis of CYP2C19 in Colombian mestizo individuals. BMC Clin Pharmacol. 2007; 7:6.

8. Cheng J.T., Chen R.M. Mechanisms of ketamine-involved regulation of cytochrome P450 gene expression. Expert Opin Drug Metab Toxicol. 2010. Mar; 6(3): 273-81.

9. Chorley B. N, Wang X., Campbell M. R., Pittman G.S., Noureddine M.A. Bell D.A. Discovery and verification of functional single nucleotide polymorphisms in regulatory genomic regions: current developing technologics. Mutat. Res. 2008; 659: 147-157.

10. Crettol S., Petrovic N., Murray M. Pharmacogenetics of phase 1 and phase 2 drug metabolism. Curr. Pharm. Des. 2010. 16(2); 204-16.

11. Daly A.K. Significance of the minor cytochrome P450 3A isoforms. Clin Pharmacokinet. 45(1):13-31; 2006.

12. Desta Z, Xu C., Oqburn E.T., Guo Y. Effects of the CYP2B6*6 allele on catalytic properties and inhibition of CYP B6 in vitro: implication for the mechanism of reduced efavirenz metabolism and other CYP 2 B6 substrates in vivo. Drug Metab Dispos. 2012. 9.

13. Evans W.E., Johnson J.A. Pharmacogenomics: the inherited basis for interindividual differences in drug response. 2001.

14. Fowler S.M., Riley R.S., Pritchard M.P.,Sutelitte M.S., Friedberg T., Wolf C.R. Amino acid 305 determines catalytic center accessibility in CYP3A4. Biochemistry. 18; 39(15):4406-14. 2000.

15. Garfinkel D. Studies on pig liver microsomes. I. Enzimic and pigment composition of different microsomal fractions. Arch Biochem. Biophys. 1958. 77. 493-509.

16. Inomata S., Nagashima A., Itagaki F., Homma M., Nishimura M., Osaka Y., Okuyama K., Tanaka E., Nakamura T., Kohda Y., Naito S., Miyabe M., Toyooka H. CYP2C19 genotype affects diazepam pharmacokinetics and emergence from general anesthesia. Clin Pharmacol Ther. 2005 Dec;78(6):647-55.

17. Ingelmen-Sundberg M. The human genome project and novel aspects of cytochrome P450 research. Toxicol. Appl. Pharmacol. 2005. 207: 52-56.

18. Kalow W., Tang B.K., Endrenyi T. Hypothesis: comparisons of inter- and intrainvolved variations can substitute for twin studies in drug research. Pharmacogenetics 1998; 8:283-289.

19. Klingenberg M. Pigments of rat liver microsomes. Arch Biochem. Biophys., 1958. 75. 376-386.

20. Khokhar J.Y., Tyndale R.F. Drug metabolism within the brain changes drug response: selective manipulation of brain CYP2B alters propofol effects. Neuropsychopharmacology. 2011. Feb. 36(3): 692-700.

21. Lamba J.K., Lin Y.S., Schuetz E.G., Thummel K.E. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Devil Rev. 2002. Nov 18. 54(10): 1271-94.

22. Lee S.J., Goldstein J.A. Functinally defective or altered CYP3A4 and CYP3A5 single nucleotide polymorphisms and their with genotyping tests. Pharmacogenomics. 2005. Jun; 6(4): 357-71.

23. Mo S.L., Liu Y.H., Duan W., Wei M.Q., Kanwar J.R., Zhou S.F. Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6. Curr Drug Metab. 2009. Sep; 10(7):730-53.

24. Mossner L.D., Schmitz A., Theurillat R., Thormann W., Mevissen M. Inhibition of cytochrome P450 enzymes involved in ketamine metabolism by use of liver microsomes and specific cytochrome P450 enzymes from horses, dogs and humans. Am J. Vet Res. 2011. Nov; 72(11): 1505-13.

25. Noppers I., Olofsen E., Niesters M., Aarts L., Mooren R., Dahan A., Kharasch E., Sarton E. Effect of rifampicin on S-ketamine and S-norketamine plasma concentrations in healthy volunteers after intravenous S-ketamine administration. Anesthesiology. 2011. Jun; 114(6): 1435-45.

26. Ogawa R., Echizen H. Drugdrug interaction profiles of proton pump inhubitors. Clin. Pharmacokinet. 2010. Aug; 49(8): 509-33.

27. Okkola K.T., Ahonen S. Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008. (182): 335-60.

28. Omura, T., Sato, R., Cooper, D.Y., Rosenthal, O., and Estebrook, K.W. Function of cytochrome P450 microsomes. Fed. Pron. 1965. 24. 1181-1189.

29. Osaka Y., Inomata S., Tanaka E., Nakamura T., Honda K., Miyabe M., Toyooka H., Tanaka M. Effect of propofol on ropivacaine metabolism in human liver microsomes. J. Anesth. 2006. 20(1):60-3.

30. Peltonieni M.A., Saari T.I., Hagelberg N.M., Reponen P, Turpeinen M., Laine K., Neuvonen P.J., Olkkola K.T. Exposure to oral S-ketamine is unaffected by itraconazole but greatly increased by ticlopidine. Clin Pharmacol Ther, 2011.

31. Phillips K.A., Veenstra D.L., Oren E. et al. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. J.A.M.A. 2001. 286: 2270-2279.

32. Restrepo J.G., Garcia-Martin I., Martinez C. et al. Polimorphic drug metabolism in anaesthesia. Curr Drug Metab. 2009. Mar; 10(3): 236-46.

33. Restrepo J.G., Martinez C., Garcia-Agurdez A. et al. Cytochrome P450 CYP2B6 genotypes and haplotypes in a colombian population: identification of novel variant CYP2B6 alleles. Pharmacogenet Genomics 2011. 21. 773-8.

34. Sugimoto M., Futura T., Nakamura A., Shirai N., Ikuma M., Misaka S., Uchida S., Watanabe H., Ohashi K., Ishizaki T., Hishida A. Maintenance time of sedative effects after an intravenous infusion of diazepam: a guide for endoscopy using diazepam. World J. Gastroenterol. 2008. Sep 7;14(33): 5197-203.

35. Yanagihara Y., Kariga S., Ohtani M., Uchino K., Aogama T., Yamamura Y. Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes. 2008.

Для цитирования:

Махарин О.А., Макляков Ю.С., Женило В.М. Полиморфизм генов системы детоксикации ксенобиотиков и его роль в биотрансформации внутривенных анестетиков. БИОМЕДИЦИНА. 2012;1(3):98-107.

For citation:

Maharin O.A., S Maklyakov Y..., Genilo V.M. Polymorphism genes of the system xenobiotics detoxycation and its role in biotransformation of intravenous anaesthetics. Journal Biomed. 2012;1(3):98-107. (In Russ.)

Просмотров: 13

Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.

ISSN 2074-5982 (Print)
ISSN 2074-5982 (Online)