Effect of CYP2C9, PTGS-1 and PTGS-2 gene polymorphisms on the efficiency and safety of postoperative analgesia with ketoprofen

Dmitry A. Sychev; Tatiana E. Morozova; Dmitry A. Shatskiy; Nadezhda V. Shikh; Evgeniya V. Shikh; Tatiana B. Andrushchyshina; Maria V. Lukina; Anastasia A. Kachanova; Zhannet A. Sozaeva; Sherzod P. Abdullaev; Natalia P. Denisenko; Kristina A. Ryzhikova

doi:10.1515/dmpt-2021-0222

Article

Effect of CYP2C9, PTGS-1 and PTGS-2 gene polymorphisms on the efficiency and safety of postoperative analgesia with ketoprofen

Dmitry A. Sychev , Tatiana E. Morozova , Dmitry A. Shatskiy , Nadezhda V. Shikh , Evgeniya V. Shikh , Tatiana B. Andrushchyshina , Maria V. Lukina , Anastasia A. Kachanova , Zhannet A. Sozaeva , Sherzod P. Abdullaev , Natalia P. Denisenko and Kristina A. Ryzhikova

Published/Copyright: June 15, 2022

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From the journal Drug Metabolism and Personalized Therapy Volume 37 Issue 4

Abstract

Objectives

Patients undergoing cardiac surgery develop post-sternotomy pain syndrome. The aim of this study was evaluation of the influence of CYP2C9, PTGS-1 and PTGS-2 genes polymorphisms on the efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery.

Methods

The study included 90 patients undergoing cardiac surgery. A real-time polymerase chain reaction was used for the detection of single nucleotide polymorphisms (SNP). Pain intensity was measured by the Numeric Rating Scale (NRS). Dyspeptic symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Acute kidney injury (AKI) was determined by Kidney Disease Improving Global Outcomes criteria.

Results

Pain intensity by the NRS score was significantly higher in patients with CYP2C9*3 АA genotype compared to АC genotype: 7 [1,10] and 6 [2,7] (p=0.003); 7 [1,10] and 6 [2,7] (p=0.04); 6 [0; 10] and 5 [2,6] (p=0.04); 5 [0; 8] and 3 [0; 8] (p=0.02), on days 1, 2, 3 and 5 in the postoperative period, respectively. GSRS score was higher in patients with CYP2C9*2 CT genotype compared to CС genotype: 19 [15; 42] and 18 [15,36] (p=0.04), respectively. There were no significant differences in the pain intensity, dyspepsia severity and AKI frequency in patients with homozygous and heterozygous genotypes for PTGS-1 rs10306135, PTGS-1 rs12353214, PTGS-2 rs20417.

Conclusions

CYP2C9*3 and CYP2C9*2 gene polymorphisms may affect efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery.

Keywords: cardiac surgery; dyspepsia; ketoprofen; pharmacogenetics; postoperative analgesia

Corresponding Author: Dmitry A. Shatskiy, PhD Student, Department of Clinical Pharmacology and Internal Diseases, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2, Trubetskaya str., Moscow, 119991, Russian Federation, Phone: +7 (965) 145-69-25, E-mail: dmshatsk@gmail.com

Acknowledgments

We would like to thank all the hospital staff and participants who were involved in the study.

Research funding: This study was financially supported by RF President’s grant for scientific schools, project № NSh 2698.2020.7
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The study was approved by the Institutional Review Board of I.M. Sechenov First Moscow State Medical University (Sechenov University), Act № 17–19, date of act 11.12.2019.

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Received: 2021-12-05

Accepted: 2022-02-04

Published Online: 2022-06-15

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Articles in the same Issue

https://doi.org/10.1515/dmpt-2021-0222

Keywords for this article

cardiac surgery; dyspepsia; ketoprofen; pharmacogenetics; postoperative analgesia