Xin Liang, Zhu Haoxiang, Niu Suping, Han Xie, Pang Hongxian, Li Jiangfan, Hu Ye, Wang Xuhong, Li Lujin, Fang Yi
Medical Institution Conducting Clinical Trials for Human Used Drug, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Center for Pharmacometrics, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pain Res (Lausanne). 2025 Jan 17;5:1474529. doi: 10.3389/fpain.2024.1474529. eCollection 2024.
The aim of this study was to establish a pharmacodynamic model of tapentadol analgesia under dose titration conditions, to quantitatively analyze the time-effect relationship of the drug, and to identify relevant influencing factors. This model is intended to provide a pharmacodynamic reference for designing rational tapentadol dose titration schemes in clinical research.
Randomized controlled trials assessing the efficacy of tapentadol in the management of chronic pain were retrieved from public databases (PubMed and EMBASE). A time-effect relationship model of the percent change in Numerical Rating Scale (NRS) scores post-tapentadol intervention from baseline was constructed, along with a covariate model to identify factors significantly impacting the analgesic effects of tapentadol. Potential influencing factors that were clinically significant but not included in the final covariate model were examined for their impact trends on tapentadol analgesia through subgroup analysis.
A total of 16 studies involving 4,508 participants were included in the analysis. Covariate analysis indicated that age significantly affected the maximum reduction in NRS scores following tapentadol treatment, with the reduction rate being 40.9% for patients aged 45 and 60.7% for those aged 65, suggesting that older patients have a higher demand for pain relief. Furthermore, studies published after 2014 and placebo-controlled trials showed a slower rate of NRS reduction, indicating a more cautious approach to tapentadol dosing titration post the U.S. opioid crisis and in placebo-controlled contexts. Additionally, subgroup analysis suggested that higher titration doses, higher baseline NRS levels, the use of extended-release tapentadol, and a smaller proportion of male participants were trends associated with better analgesic effects, although the differences were not statistically significant. Moreover, the study found that tapentadol was significantly more effective in treating lower back pain compared to non-lower back pain.
This research successfully developed a pharmacodynamic model for dose-titrated tapentadol administration, which can simulate the temporal changes in analgesic effects of tapentadol across different clinical scenarios. This model can guide the formulation of dosing titration protocols for tapentadol in clinical research.
本研究旨在建立剂量滴定条件下曲马多镇痛的药效学模型，定量分析药物的时效关系，并确定相关影响因素。该模型旨在为临床研究中设计合理的曲马多剂量滴定方案提供药效学参考。
从公共数据库（PubMed和EMBASE）检索评估曲马多治疗慢性疼痛疗效的随机对照试验。构建了曲马多干预后数字评分量表（NRS）评分相对于基线变化百分比的时效关系模型，以及一个协变量模型，以确定对曲马多镇痛效果有显著影响的因素。通过亚组分析，研究了临床上具有显著意义但未纳入最终协变量模型的潜在影响因素对曲马多镇痛的影响趋势。
共有16项研究、4508名参与者纳入分析。协变量分析表明，年龄显著影响曲马多治疗后NRS评分的最大降低幅度，45岁患者的降低率为40.9%，65岁患者为60.7%，这表明老年患者对疼痛缓解的需求更高。此外，2014年后发表的研究和安慰剂对照试验显示NRS降低速度较慢，这表明在美国阿片类药物危机后以及在安慰剂对照的情况下，曲马多剂量滴定应更加谨慎。此外，亚组分析表明，较高的滴定剂量、较高的基线NRS水平、使用缓释曲马多以及男性参与者比例较小与更好的镇痛效果相关，尽管差异无统计学意义。此外，研究发现，与非下背部疼痛相比，曲马多治疗下背部疼痛的效果显著更好。
本研究成功建立了曲马多剂量滴定给药的药效学模型，该模型可以模拟曲马多在不同临床场景下镇痛效果的时间变化。该模型可指导临床研究中曲马多给药滴定方案的制定。
