• J Pain Symptom Manage · Jan 2024

    Comparative Study

    Comparison of the effects of OPRM1 A118G polymorphism using different opioids: A prospective study.

    • Miho Takemura, Kazuyuki Niki, Yoshiaki Okamoto, Tomohiro Kawamura, Makie Kohno, Yoshinobu Matsuda, and Kenji Ikeda.
    • Department of Clinical Pharmacy Research and Education (M.T., K.N., K.I.), Osaka University Graduate School of Pharmaceutical Sciences, Suita, Osaka, Japan; Department of Pharmacy (M.T., K.N., Y.O.), Ashiya Municipal Hospital, Ashiya, Hyogo, Japan. Electronic address: takemura-m@phs.osaka-u.ac.jp.
    • J Pain Symptom Manage. 2024 Jan 1; 67 (1): 3949.e539-49.e5.

    Contextμ-opioid receptor gene (OPRM1) A118G polymorphism (rs1799971) causes loss of N-glycosylation sites at the extracellular domain of μ-opioid receptors. G-allele carriers show a limited response to morphine; however, studies investigating the impact of A118G polymorphism on the efficacy of opioids other than morphine are limited.ObjectiveTo compare the impact of A118G polymorphism on the efficacy of various opioids.MethodsThis prospective cohort study enrolled 222 in-patients administered one of the following opioid therapies for cancer pain as part of an opioid introduction or rotation strategy: tapentadol extended-release tablets, methadone tablets, hydromorphone controlled-release tablets, oxycodone controlled-release tablets, or transdermal fentanyl patches. The impact of A118G polymorphism on the difference in the Brief Pain Inventory-Short Form score on days three, seven, and 14 from baseline was compared among the groups.ResultsOverall, 81, 74, and 67 patients had the AA, AG, and GG genotypes, respectively, with an OPRM1 A118G G-allele variant frequency of 0.47. The reduction in the Brief Pain Inventory-Short Form score after opioid therapy initiation did not differ significantly among the patients with the three A118G genotypes treated with tapentadol (p = 0.84) or methadone (p = 0.97), whereas it was significantly smaller in G-allele carriers than that in AA homozygous patients treated with hydromorphone (p < 0.001), oxycodone (p = 0.031), or fentanyl (p < 0.001).ConclusionTapentadol and methadone may be more suitable than hydromorphone, oxycodone, and fentanyl for G-allele carriers due to their dual mechanism of action and low susceptibility to OPRM1 A118G polymorphism.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

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