Effect of genetic polymorphisms and haplotypes on the efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery

Abstract Background Most cardiac surgeries are associated with post-sternotomy pain syndrome. Pain causes elevation of blood pressure, heart rate and may be hemodynamic instability, respiratory infections, other postoperative complications. Non-steroidal anti-inflammatory drugs (NSAIDs) among the most commonly used analgesics in surgery. The majority NSAIDs metabolized by cytochrome P-450. mechanism action is blocking prostaglandin-endoperoxide synthase (PTGS). Individual variabilities gene polymorphisms affect ketoprofen exposure, efficacy safety. Purpose Evaluation influence CYP2C9 - CYP2D6 PTGS-2 rs20417 – PTGS-1 rs12353214 haplotypes on safety analgesia patients coronary artery disease after Methods study included 90 patients. intensity assessment was measured Numeric Rating Scale (NRS). Dyspeptic symptoms were evaluated using Gastrointestinal Symptom (GSRS). Acute kidney injury determined Kidney Disease Improving Global Outcomes criteria. Genotyping CYP2C9*3 (1075A>C) rs1057910, CYP2D6*4 (1846G>A) rs3892097, (G>C) rs20417, (C>T) performed. Results revealed following haplotypes: (1) rs1057910 (AA) rs3892097 (GG), (2) (AC) (GA), (3) (GG) (CT), (4) (CC) (CC). NRS score significantly higher AA-GG haplotype compared to AC-GA for CYP2D6*4: 7,13±2,14 5±1,52 (p=0,009); 7,06±1,99 4,86±1,57 (p=0,007); 4,96±1,83 3,29±1,79 (p=0,04); 4,57±1,66 2,86±1,57 (p=0,02), days 1, 2, 3 5 period, respectively. There no significant differences haplotypes. Also there GSRS acute frequency GG-CT CC-CC rs12353214. Conclusion Further studies needed develop genotype-guided management. Funding Acknowledgement Type funding sources: Public grant(s) National budget only. Main source(s): This financially supported RF President's grant scientific schools, project No. NSh 2698.2020.7 NRSDyspepsia