Department of Pharmacology & Therapeutics, Shifa College of Medicine, Shifa Tameer-e-Millat University, Islamabad, Pakistan.
Department of Pharmacology & Therapeutics, Basic Medical Sciences Institute, JPMC, Karachi, Pakistan.
PLoS One. 2022 May 13;17(5):e0266559. doi: 10.1371/journal.pone.0266559. eCollection 2022.
Gabapentinoids are the first-line drugs for neuropathic pain. These drugs are the substrate of organic cation transporter (OCTN1) for renal excretion and absorption across the intestinal epithelium. Gabapentinoids exhibit wide interindividual variability in daily dosage and therapeutic efficacy which makes titration regimens prolonged for optimal efficacy. The present study aimed to investigate the possible influence of the single nucleotide polymorphism (SNP) of OCTN1 on therapeutic efficacy and safety of gabapentinoids in neuropathic pain patients of the Pakistani population.
Four hundred and twenty-six patients were enrolled in the study. All participants were genotyped for OCTN1 rs1050152 and rs3792876 by PCR-RFLP method and followed up for eight weeks. The therapeutic outcomes of gabapentinoids, reduction in pain score, inadequate or complete lack of response, adverse events (AEs) in responders and discontinuation of treatment on account of AEs were recorded for all patients.
There was no significant association of genotypes and alleles of both SNPs on the clinical response of gabapentinoids (P ˃ 0.05). Similarly, significant differences were not found in the reduction of pain scores and AEs among different genotypes in the responders. The present study has reported the association of OCTN1 rs1050152 and rs3792876 polymorphisms with clinical outcomes of gabapentinoids for the first time in the real-world clinical setting.
Our results suggest a lack of influence of OCTN1 genetic variants in the determination of clinical response to gabapentinoids in patients with neuropathic pain in the Pakistani population. These findings signify the role of renal functions in predicting the interindividual variability to therapeutic responsiveness of gabapentinoids.
加巴喷丁类药物是治疗神经性疼痛的一线药物。这些药物是有机阳离子转运体（OCTN1）的底物，通过肾脏排泄和肠上皮吸收。加巴喷丁类药物在每日剂量和治疗效果方面表现出广泛的个体间变异性，这使得为达到最佳疗效而延长了滴定方案。本研究旨在探讨 OCTN1 单核苷酸多态性（SNP）对巴基斯坦人群神经性疼痛患者加巴喷丁类药物治疗效果和安全性的可能影响。
本研究纳入了 426 名患者。所有参与者均通过 PCR-RFLP 方法对 OCTN1 rs1050152 和 rs3792876 进行基因分型，并随访 8 周。记录所有患者加巴喷丁类药物的治疗效果、疼痛评分降低、反应不足或完全缺乏反应、应答者的不良反应（AE）以及因 AE 而停止治疗的情况。
两种 SNP 的基因型和等位基因与加巴喷丁类药物的临床反应均无显著相关性（P ˃ 0.05）。同样，在应答者中，不同基因型之间的疼痛评分降低和 AE 也没有显著差异。本研究首次在真实临床环境中报告了 OCTN1 rs1050152 和 rs3792876 多态性与加巴喷丁类药物临床疗效的关联。
我们的结果表明，在巴基斯坦人群中，OCTN1 遗传变异对神经性疼痛患者加巴喷丁类药物临床反应的影响不大。这些发现表明，肾功能在预测加巴喷丁类药物治疗反应的个体间变异性方面起着重要作用。
