The relationship of postoperative tramadol activity with the CYP2D6*17 genome in total knee artroplasty patients

Yıl 2024, Cilt: 17 Sayı: 2, 237 - 242, 01.04.2024

Nusret Ök , Muhammet Erdi Gürbüz , Aylin Koseler

https://doi.org/10.31362/patd.1351539

Öz

Purpose: In our study, we examined the effect of tramadol maintenance on the VAS score in geriatric patients. We observed them until the postoperative 60th minute. We investigated the incidence of pain in patients who underwent knee arthroplasty in the study. Our aim was to examine the effect of the *17 allele of the CYP2D6 genome on postoperative tramadol activity.
Materials and methods: In our study we examined 110 patients who underwent total knee arthroplasty in the Department of Orthopedics and Traumatology at our facility, along with 100 healthy individuals without complaints who served as the control group. Each patient received a 100 mg dose of intravenous tramadol (Contramal). The postoperative VAS scores of the patients were recorded at 0-15-30-45-60 minutes.
Results: The average age of the patients was 62.36 years. In our study, 86.4% of the patients were female, while this rate was 46% in the control group. We found that 3.65% of individuals (*17 carriers) possessed the *17 allele in both the patient group (n=7) and the control group (n=7). At the postoperative 0th minute, the VAS score for patients in the *1/*1 group was 91.07, while for the *1/*17 group, it measured 95.0. There was no statistically significant difference between the genomes (p>0.050). Likewise, no statistically significant difference was found between the genomes at the postoperative 15th, 30th, 45th, and 60th minutes (p>0.050). However, we observed a statistically significant decrease in the postoperative VAS score between 0-60 minutes in both groups, indicating time-dependent variation (p=0.000).
Conclusion: When examining diverse literature on tramadol classification as intermediate metabolizer (IM) or extensive metabolizer (EM) concerning the *17 allele, our study indicates that the *17 allele should be regarded as both extensive metabolizer (EM) and normal metabolizer (NM).

Anahtar Kelimeler

Total knee arthroplasty CYP2D6, Tramadol, CYP2D6*1/*17, postoperartive pain

Total diz artroplastisi uygulanan hastalarda postoperatif tramadol etkinliğinin CYP2D6*17 genomu ilişkisi

Öz

Amaç: Geriatrik hastalarda tramadol idamesinin VAS skoruna etkisini incelediğimiz çalışmamızda ameliyat sonrası 60. dakikaya kadar gözlem yaptık. Çalışmada diz artroplastisi uygulanan hastalarda ağrı insidansını araştırdık. Ameliyat sonrası tramadol etkinliğine CYP2D6 genomunun *17 alelinin etkisini incelemeyi amaçladık.
Gereç ve yöntem: Bu çalışmaya Pamukkale Üniversitesi Tıp Fakültesi Ortopedi ve Travmatoloji Anabilim Dalı’nda servisimize total diz antroplastisi uygulanan 110 hasta ve kontrol grubu olarak şikâyeti olmayan sağlıklı 100 kişi dahil edildi. Her hastaya intravenöz yoldan 100 mg Tramadol (contramal) uygulandı. Hastaların post-op 0-15-30-45-60. dk VAS skorları kaydedildi.
Bulgular: Hastalar ortalama 62,36 yaşındaydı. Çalışmamızdaki hastaların %86,4’ü kadınken kontrol grubunda bu oran %46 olarak bulundu. *17 alelinin varlığı hasta (n=7) ve kontrol grubunda (n=7) toplamda %3,65 oranında (n=14) *17 taşıyıcısına rastladık. VAS postoperartive 0. dakikada *1/*1 grubundaki hastaların VAS skoru 91,07 ve *1/*17 genomunun VAS skoru 95,0 şeklindeydi ve genomlar arasında istatistiksel olarak anlamlı bir farklılık yoktu (p>0,050). Benzer şekilde ameliyat sonrası 15., 30., 45. ve 60. dakikada da genomlar arasında istatistiksel olarak anlamlı bir farklılık yoktu (p>0,050). Zamana bağlı değişimde her iki gruptada post-op VAS skorunun 0-60 dakika arasında istatistiksel olarak anlamlı şekilde düştüğünü gördük (p=0,000).
Sonuç: Tramadolun *17 aleli ile ilişkisinde IM veya EM olarak sınıflandırıldığı literatürdeki farklı sonuçlar alınmış çalışmaları incelediğimizde bizim çalışmamızın sonuçlarına göre: *17 aleli EM ile NM şeklinde değerlendirilmesi gerektiğini düşünüyoruz.

Anahtar Kelimeler

Total diz artroplastisi, CYP2D6, Tramadol, CYP2D6*1/*17, ameliyat sonrası ağrı

Kaynakça

• 1. Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinetics 2004;43:879-923. https://doi.org/10.2165/00003088-200443130-00004
• 2. Scott LJ, Perry CM. Tramadol: a review of its use in perioperative pain. Drugs 2000;60:139-176. https://doi.org/10.2165/00003495-200060010-00008
• 3. Lintz W, Barth H, Osterloh G, Schmidt Böthelt E. Bioavailability of enteral tramadol formulations. 1st communication: capsules. Arzneimittelforschung 1986;36:1278-1283.
• 4. Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance. Clin Pharmacokinet 2009;48:761-804. https://doi.org/10.2165/11318070-000000000-00000
• 5. Stamer UM, Musshoff F, Kobilay M, Madea B, Hoeft A, Stuber F. Concentrations of tramadol and O‐desmethyltramadol enantiomers in different CYP2D6 genotypes. Clin Pharmacol Ther 2007;82:41-47. https://doi.org/10.1038/sj.clpt.6100152
• 6. Payne K, Roelofse J, Shipton E. Pharmacokinetics of oral tramadol drops for postoperative pain relief in children aged 4 to 7 years--a pilot study. Anesth Prog 2002;49:109-112.
• 7. Gong L, Stamer UM, Tzvetkov MV, Altman RB, Klein TE. Pharm GKB summary: tramadol pathway. Pharmacogenet Genomics 2014;24:374-380. https://doi.org/10.1097/FPC.0000000000000057
• 8. Bell KL, Shohat N, Goswami K, Tan TL, Kalbian I, Parvizi J. Preoperative opioids increase the risk of periprosthetic joint infection after total joint arthroplasty. J Arthroplasty 2018;33:3246-3251. https://doi.org/10.1016/j.arth.2018.05.027
• 9. Ben Ari A, Chansky H, Rozet I. Preoperative opioid use is associated with early revision after total knee arthroplasty: a study of male patients treated in the veterans affairs system. J Bone Joint Surg Am 2017;99:1-9. https://doi.org/10.2106/JBJS.16.00167
• 10. Goplen CM, Verbeek W, Kang SH, et al. Preoperative opioid use is associated with worse patient outcomes after total joint arthroplasty: a systematic review and meta-analysis. BMC Musculoskelet Disord 2019;20:234. https://doi.org/10.1186/s12891-019-2619-8
• 11. Bravo L, Mico JA, Berrocoso E. Discovery and development of tramadol for the treatment of pain. Expert Opin Drug Discov 2017;12:1281-1291. https://doi.org/10.1080/17460441.2017.1377697
• 12. April KT, Bisaillon J, Welch V, et al. Tramadol for osteoarthritis. CDSR 2019: CD005522(e1-102). https://doi.org/10.1002/14651858.CD005522.pub3
• 13. Shen H, He MM, Liu H, et al. Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17. Drug Metab Dispos 2007;35:1292-1300. https://doi.org/10.1124/dmd.107.015354
• 14. Dagostino C, Allegri M, Napolioni V, et al. CYP2D6 genotype can help to predict effectiveness and safety during opioid treatment for chronic low back pain: results from a retrospective study in an Italian cohort. Pharmacogenomics and personalized medicine. Pharmgenomics Pers Med 2018;11:179-191. https://doi.org/10.2147/PGPM.S181334
• 15. Magarbeh L, Gorbovskaya I, Le Foll B, Jhirad R, Müller DJ. Reviewing pharmacogenetics to advance precision medicine for opioids. Biomed Pharmacother 2021;142:112060. https://doi.org/10.1016/j.biopha.2021.112060
• 16. Lopes GS, Bielinski SJ, Moyer AM, et al. Sex differences in associations between CYP2D6 phenotypes and response to opioid analgesics. Pharmgenomics Pers Med 2020;13:71-79. https://doi.org/10.2147/PGPM.S239222
• 17. Kirchheiner J, Schmidt H, Tzvetkov M, et al. Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication. Pharmacogenomics J 2007;7:257-265. https://doi.org/10.1038/sj.tpj.6500406
• 18. Aynacioglu AS, Sachse C, Bozkurt A, et al. Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population. Clin Pharmacol Ther 1999;66:185-192. https://doi.org/10.1053/cp.1999.v66.100072001
• 19. Oscarson M, Hidestrand M, Johansson I, Ingelman Sundberg M. A combination of mutations in the CYP2D6* 17 (CYP2D6Z) allele causes alterations in enzyme function. Mol. Pharmacol. 1997;52:1034-1040. https://doi.org/10.1124/mol.52.6.1034
• 20. Masimirembwa C, Persson I, Bertilsson L, Hasler J, Ingelman Sundberg M. A novel mutant variant of the CYP2D6 gene (CYP2D6 17) common in a black African population: association with diminished debrisoquine hydroxylase activity. Br J Clin Pharmacol 1996;42:713-719. https://doi.org/10.1046/j.1365-2125.1996.00489.x
• 21. Hua Gan S, Ismail R, Adnan WAW, Zulmi W. Impact of CYP2D6 genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics. Mol Diagn Ther 2007;11:171-181. https://doi.org/10.1007/BF03256239
• 22. Subrahmanyam V, Renwick AB, Walters DG, et al. Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. Drug Metab Dispos 2001;29:1146-1155.
• 23. Halling J, Weihe P, Brosen K. CYP2D6 polymorphism in relation to tramadol metabolism: a study of faroese patients. Ther Drug Monit 2008;30:271-275. https://doi.org/10.1097/FTD.0b013e3181666b2f
• 24. Kirchheiner J, Keulen JTH, Bauer S, Roots I, Brockmöller J. Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. J Clin Psychopharmacol 2008;28:78-83. https://doi.org/10.1097/JCP.0b013e318160f827