Department of Pharmacy, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, China.
Department of Pharmacy, Wuhan No. 1 Hospital, Wuhan 43002, China.
Eur J Pharm Sci. 2024 Jun 1;197:106777. doi: 10.1016/j.ejps.2024.106777. Epub 2024 Apr 20.
Diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN) are challenging and often intractable complex medical conditions, with a substantial impact on the quality of life. Mirogabalin, a novel voltage-gated Ca channel α2δ ligand, was approved for the indication of DPNP and PHN. However, the time course of effects has not yet been clarified.We aimed to establish pharmacodynamic and placebo effect models of mirogabalin and pregabalin in DPNP and PHN, and to quantitatively compare the efficacy characteristics (maximum efficacy, onset time, and other pharmacodynamic parameters) and safety of mirogabalin and pregabalin. Public databases were comprehensively searched for randomized placebo-controlled clinical trials. A model-based meta-analysis (MBMA) was developed to describe the time course of drug efficacy and placebo effects. Adverse events were compared using a fixed-effects meta-analysis. Sixteen studies including 5,147 participants were eligible for this study. The placebo effect was relatively high and gradually increased with time, and it required at least eight weeks to reach a plateau. The pharmacodynamic model revealed that the maximum pure efficacy for mirogabalin and pregabalin was approximately -7.85 % and -8.86 %, respectively; the efficacy of mirogabalin to relieve DPNP and PHN was not superior to that of pregabalin, and both drugs had similar safety. While the rate constant of the onset rate of pregabalin was approximately thrice as high as that of mirogabalin. In addition, the baseline level of pain was an important factor affecting pregabalin efficacy. These findings are helpful in evaluating the clinical extension value of mirogabalin. They suggest that the high placebo effect and the baseline level of pain should be considered when grouping patients in future research and development of voltage-gated Ca channel neuroanalgesic.
糖尿病周围神经性疼痛（DPNP）和带状疱疹后神经痛（PHN）是具有挑战性且常难以治疗的复杂医学病症，对生活质量有重大影响。米罗 gabalin 是一种新型电压门控钙通道 α2δ 配体，已获批用于治疗 DPNP 和 PHN。然而，其疗效的时间过程尚未明确。我们旨在建立 DPNP 和 PHN 中米罗 gabalin 和普瑞巴林的药效学和安慰剂效应模型，并定量比较米罗 gabalin 和普瑞巴林的疗效特征（最大疗效、起效时间和其他药效学参数）和安全性。我们全面检索了公共数据库中的随机安慰剂对照临床试验。采用基于模型的荟萃分析（MBMA）来描述药物疗效和安慰剂效应的时间过程。采用固定效应荟萃分析比较不良反应。纳入了 16 项研究共 5147 名参与者。安慰剂效应相对较高，且随时间逐渐增加，需要至少 8 周才能达到平台期。药效学模型显示，米罗 gabalin 和普瑞巴林的最大纯疗效分别约为-7.85%和-8.86%；米罗 gabalin 缓解 DPNP 和 PHN 的疗效并不优于普瑞巴林，且两种药物的安全性相当。此外，普瑞巴林起效速率常数约为米罗 gabalin 的三倍。此外，疼痛基线水平是影响普瑞巴林疗效的重要因素。这些发现有助于评估米罗 gabalin 的临床扩展价值。它们表明，在未来电压门控钙通道神经镇痛药的研发中，应考虑高安慰剂效应和疼痛基线水平，对患者进行分组。
