Pharmacogenetic Unit, Clinical Pharmacology Department, Alicante Institute for Health and Biomedical Research (ISABIAL), General University Hospital of Alicante, c/Pintor Baeza, 12, 03010 Alicante, Spain.
Clinical Pharmacology, Toxicology and Chemical Safety Unit, Institute of Bioengineering, Miguel Hernández University, Avda. de la Universidad s/n, 03202 Elche, Spain.
Int J Mol Sci. 2023 Jun 28;24(13):10754. doi: 10.3390/ijms241310754.
Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients ( = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by , μ-opioid receptor (), and catechol-O-methyl transferase () genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, < 0.01) by improving pain relief (28 vs. 48 mm, < 0.05), increased quality of life (43 vs. 56 mm < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1-5] vs. 1 [0-2], < 0.01) and 42% opioid dose (35 [22-61] vs. 60 [40-80] mg/day, < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58-0.82] vs. 0.51 [0.13-0.67] controls, < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30-34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation.
个体间镇痛反应的变异性至少部分归因于已明确特征的多态性，这些多态性与阿片类药物剂量和不良结局相关。临床药物遗传学实施联盟（CPIC）已提出了表型的建议，但研究药物-基因对的清单仍在不断增加。这项临床试验将慢性疼痛患者（n=60）随机分为两组，一组接受根据μ-阿片受体（）和儿茶酚-O-甲基转移酶（）基因型指导的阿片类药物处方，另一组接受常规临床治疗。与常规临床治疗组相比，基因型指导治疗降低了疼痛强度（76 对 59mm，<0.01），提高了疼痛缓解程度（28 对 48mm，<0.05），改善了生活质量（43 对 56mm，<0.001），降低了临床相关不良事件的发生率（3 [1-5] 对 1 [0-2]，<0.01）和 42%的阿片类药物剂量（35 [22-61] 对 60 [40-80]mg/天，<0.05）。与常规处方组相比，最终健康效用评分显著更高（0.71 [0.58-0.82] 对 0.51 [0.13-0.67]，<0.05），改善了困倦和抑郁共病情况，头痛、口干、紧张和便秘的发生率降低了 30-34%。大规模实施分析有助于临床转化，并结合药物经济学评估。
