The effect of CYP2D6 and CYP2C9 gene polymorphisms on the efficacy and safety of the combination of tramadol and ketorolac used for postoperative pain management in patients after video laparoscopic cholecystectomy.
OBJECTIVES
One of the key components of ERAS is adequate pain control in the postoperative period. There are no rational schemes for postoperative pain relief. At the same time, adequate postoperative pain relief promotes early activation and early rehabilitation of patients and shortens the duration of the postoperative stay, and does not cause postoperative complications associated with analgesia (weakness, intestinal paresis, nausea and vomiting). The aims of the present study are to assess the possible association of CYP2D6 and CYP2C9 polymorphisms with the efficacy and safety of tramadol and ketorolac in postoperative pain.


METHODS
A total of 107 patients were genotyped for CYP2D6 and CYP2C9 polymorphisms. All patients underwent laparoscopic cholecystectomy. Postoperative pain relief was carried out with ketorolac and tramadol. Postoperative pain syndrome was assessed using a visual analogue scale and McGill pain questionnaire. The profile of side effects was assessed by the dynamics of red blood counts as a possible trigger for the development of gastrointestinal bleeding according to the method of global assessment of triggers.


RESULTS
Pain was statistically significantly lower in CYP2C9*2 carriers, according to visual analogue scale (VAS): after 12 h - by 1.5 (p=0.002); after 24 h - by 1.1 (p=0.012); after 36 h - by 1.05 (p=0.004); after 48 h - by 0.7 (p=0.026). In CYP2C9*3 carriers the results were not statistically significant. In carriers of CYP2D6*4 pain syndromes were higher at all-time intervals, but statistically reliable results were obtained only after 2 h - by 1.01 (p=0.054) and after 24 h - by 0.8 (p=0.035). The profile of adverse reactions for NSAIDs was evaluated by the dynamics of hemoglobin and erythrocyte indices. A more pronounced decrease in the relative difference in hemoglobin levels was noted in CYP2C9*2 and CYP2C9*3 polymorphism carriers - by 1.7 (p=0.00268) and-by 2.2 (p=0.000143), respectively.


CONCLUSIONS
CYP2D6 and CYP2C9 can predict analgesic effectiveness of tramadol and ketorolac. CYP2C9 can predict the risk of gastrointestinal bleeding, including those hidden to ketorolac.
['Muradian|Andranik Alexandrovich|AA|https://orcid.org/0000-0003-4367-637X', 'Sychev|Dmitry Alekseevich|DA|https://orcid.org/0000-0002-4496-3680', 'Blagovestnov|Dmitry Alekseevich|DA|https://orcid.org/0000-0001-5724-6034', 'Sozaeva|Zhannet Alimovna|ZA|https://orcid.org/0000-0001-5166-7903', 'Akmalova|Kristina Anatolyevna|KA|https://orcid.org/0000-0003-3505-8520', 'Zastrozhin|Michael Sergeevich|MS|https://orcid.org/0000-0003-0607-4812', 'Kerimova|Leyla Nabievna|LN|', 'Koroshvili|Vadim Teymurazovich|VT|https://orcid.org/0000-0002-1613-1203', 'Epifanova|Irina Alexandrovna|IA|']
CYP2D6 CYP2C9 tramadol ketorolac non-steroidal anti-inflammatory drugs (NSAIDs) pharmacogenetics