rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2021-08-12rpcardio-2539Research ArticleNOTES FROM PRACTICEКЛИНИЧЕСКИЙ ОПЫТEvaluation of the Influence of CYP2C9* 2, CYP2C9*3 Gene Polymorphisms on the Efficacy and Safety of Postoperative Analgesia with Ketoprofen in Patients after Cardiac SurgeryОценка влияния полиморфизмов CYP2C9*2, CYP2C9*3 на эффективность и безопасность послеоперационного обезболивания кетопрофеном у больных после кардиохирургических вмешательствhttps://orcid.org/0000-0002-3748-8180МорозоваТ. Е.MorozovaT. E.

Морозова Татьяна Евгеньевна

eLibrary  SPIN  7917-1951

Москва

Tatiana E. Morozova

eLibrary  SPIN  7917-1951

Moscow

https://orcid.org/0000-0002-2068-2470ШацкийД. А.ShatskyD. A.

Шацкий Дмитрий Андреевич

Москва

Dmitry A. Shatsky

Moscow

dmshatsk@gmail.comhttps://orcid.org/0000-0002-0087-1848ШихН. В.ShikhN. V.

Ших Надежда Валерьевна

eLibrary SPIN 4950-7164

Москва

Nadezhda V. Shikh

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Moscow

https://orcid.org/0000-0001-6589-7654ШихЕ. В.ShikhE. V.

Ших Евгения Валерьевна

 eLibrary SPIN 2397-8414

Москва

 

Evgeniya V. Shikh

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Moscow

https://orcid.org/0000-0001-7940-4443АндрущишинаТ. Б.AndrushchyshinaT. B.

Андрущишина Татьяна Борисовна

eLibrary  SPIN  7738-6523

Москва

Tatiana B. Andrushchyshina

eLibrary  SPIN  7738-6523

Moscow

https://orcid.org/0000-0003-0032-2651ЛукинаМ. В.LukinaM. V.

Лукина Мария Владимировна

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Москва

Maria V. Lukina

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Moscow

 

https://orcid.org/0000-0003-3194-4410КачановаА. А.KachanovaA. A.

Качанова Анастасия Алексеевна

 eLibrary SPIN 1214-8156

Москва

Anastasia A. Kachanova

eLibrary SPIN 1214-8156

Moscow

https://orcid.org/0000-0001-5166-7903СозаеваЖ. А.SozaevaZh. A.

Созаева Жаннет Алимовна

eLibrary SPIN 4138-4466

Москва

Zhannet A. Sozaeva

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Moscow

https://orcid.org/0000-0002-5031-0088ШуевГ. Н.ShuevG. N.

Шуев Григорий Николаевич

eLibrary SPIN 4172-1330

Москва

Grigorii N. Shuev

 eLibrary SPIN 4172-1330

Moscow

https://orcid.org/0000-0003-3278-5941ДенисенкоН. П.DenisenkoN. P.

Денисенко Наталья Павловна

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Natalia P. Denisenko

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https://orcid.org/0000-0002-5621-8266ГришинаЕ. А.GrishinaE. A.

Гришина Елена Анатольевна

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Elena A. Grishina

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https://orcid.org/0000-0002-4496-3680СычевД. А.SychevD. A.

Сычев Дмитрий Алексеевич

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Dmitry A. Sychev

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Moscow

Первый Московский государственный медицинский университет им. И.М. СеченоваРоссияI.M. Sechenov First Moscow State Medical UniversityRussian FederationРоссийская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuing Professional EducationRussian Federation202102092021174570575Copyright © Morozova T.E., Shatsky D.A., Shikh N.V., Shikh E.V., Andrushchyshina T.B., Lukina M.V., Kachanova A.A., Sozaeva Z.A., Shuev G.N., Denisenko N.P., Grishina E.A., Sychev D.A., 20212021Морозова Т.Е., Шацкий Д.А., Ших Н.В., Ших Е.В., Андрущишина Т.Б., Лукина М.В., Качанова А.А., Созаева Ж.А., Шуев Г.Н., Денисенко Н.П., Гришина Е.А., Сычев Д.А.Morozova T.E., Shatsky D.A., Shikh N.V., Shikh E.V., Andrushchyshina T.B., Lukina M.V., Kachanova A.A., Sozaeva Z.A., Shuev G.N., Denisenko N.P., Grishina E.A., Sychev D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/2539Aim

Aim. The aim of the study was to evaluate the efficacy and safety of ketoprofen as an analgesic therapy in patients with CYP2C9*2 (430C>T) rs179985 and CYP2C9*3 (1075A>C) rs1057910 gene polymorphisms after cardiac surgery.

Material and methods

Material and methods. The study included 90 patients. Postoperative analgesia was perfomed by ketoprofen 100 mg intramuscularly twice daily. The evaluation of pain was determined daily by Numeric Rating Scale for 5 days after cardiac surgery. The safety of ketoprofen was determined by assessing the severity of gastroenterological symptoms using the Gastrointestinal Symptom Rating Scale questionnaire and determining the frequency of episodes of acute kidney injury. The material for DNA was venous blood. To determine the single nucleotide genetic polymorphisms CYP2C9*2 (430C>T) rs179985 and CYP2C9*3 (1075A>C) rs1057910, the real-time polymerase chain reaction was used.

Results

Results. In patients with the AA genotype of CYP2C9*3 polymorphism, the intensity of pain on the numeric rating scale scale (points) was significantly higher than in patients with the AC genotype: 7 [6; 8] vs 6 [5; 6] (р=0,003), 7 [6; 8] vs 6 [5; 6] (р=0,04), 6 [5; 7] vs 5 [4; 5] (р=0,04), 5 [3; 6] vs 3 [3; 4] points (р=0,02) on days 1, 2, 3 and 5 of the postoperative period, respectively. The severity of gastroenterological symptoms was higher in patients with a heterozygous CT genotype for the allelic variant CYP2C9*2 than in patients with a wild CС genotype and amounted to 19 [19; 22] vs 18 [16; 20] points, respectively, (p=0,04). The distribution of genotypes for CYP2C9*2 polymorphisms and CYP2C9*3 polymorphisms between the groups of acute renal injury did not differ significantly.

Conclusion

Conclusion. Associations of polymorphisms CYP2C9*3 with a lower intensity of pain syndrome and CYP2C9*2 with a greater severity of gastroenterological symptoms were revealed.

Цель

Цель. Изучить эффективность и безопасность кетопрофена в качестве обезболивающей терапии в зависимости от генетических полиморфизмов CYP2C9*2 (430C>Т) rs179985 и CYP2C9*3 (1075А>С) rs1057910 у больных в послеоперационном периоде после кардиохирургических вмешательств.

Материал и методы

Материал и методы. В исследование включены 90 пациентов. Послеоперационное обезболивание после кардиохирургических вмешательств проводилось с применением кетопрофена в дозе 100 мг внутримышечно 2 р/сут. Эффективность обезболивания определяли ежедневно с помощью цифровой рейтинговой шкалы (ЦРШ) в течение 5 сут послеоперационного периода. Безопасность применения кетопрофена определяли посредством оценки выраженности гастроэнтерологических симптомов с помощью опросника Gastrointestinal Symptom Rating Scale и определения частоты эпизодов острого почечного повреждения на 7-е сут послеоперационного периода. Материалом для выделения ДНК служила венозная кровь. Для определения однонуклеотидных генетических полиморфизмов CYP2C9*2 (430C>Т) rs179985 и CYP2C9*3 (1075А>С) rs1057910 использовался метод полимеразной цепной реакции в реальном времени.

Результаты

Результаты. У больных с генотипом АА по аллельному варианту CYP2C9*3 интенсивность боли по шкале ЦРШ была статистически значимо выше, чем у больных с генотипом АC: 7 [6; 8] против 6 [5; 6] балла (р=0,003), 7 [6; 8] против 6 [5; 6] балла (р=0,04), 6 [5; 7] против 5 [4; 5] балла (р=0,04), 5 [3; 6] против 3 [3; 4] балла (р=0,02) на 1, 2, 3 и 5 сут послеоперационного периода соответственно. Выраженность гастроэнтерологических симптомов оказалась выше у пациентов с гетерозиготным генотипом CT по аллельному варианту CYP2C9*2, чем у больных с генотипом CС, и составила 19 [19; 22] и 18 [16; 20] баллов соответственно, (р=0,04). Распределение генотипов по полиморфизмам CYP2С9*2 и CYP2C9*3 между группами острого почечного повреждения статистически значимо не различалось.

Заключение

Заключение. Выявлены ассоциации полиморфизма CYP2C9*3 с меньшей интенсивностью болевого синдрома и CYP2С9*2 с большей выраженностью гастроэнтерологических симптомов.

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The authors declare that there are no conflicts of interest present.