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Abstract：
Quantitative information is scarce with regard to guidelines for currently prescribed medications for constipation. Furthermore, these guidelines do not reflect the differences in the number of bowel movements caused by each drug.
In this study, we used a model-based meta-analysis to quantitatively estimate the deviations from the baseline number of spontaneous bowel movements (SBMs) and complete spontaneous bowel movements (CSBMs) associated with pharmacotherapy for chronic constipation to bridge the knowledge gap in the guidelines for current medications.
A comprehensive survey was conducted using literature databases. In this study, we also included randomized placebo-controlled trials on chronic constipation. Pharmacodynamic models were established to describe the time course of the numbers of SBMs and CSBMs produced by each drug.
Data from 20 studies (comprising 9998 participants and 8 drugs) were used to build this model. The results showed that bisacodyl had the greatest effect on increasing the frequency of bowel movements, whereas plecanatide yielded the lowest increase in the number of SBMs and CSBMs. After eliminating the placebo effect, the maximal increase in bowel movement frequency associated with bisacodyl was 6.8 for SBMs (95% confidence interval: 6.1-7.6) and 4.7 for CSBMs (95% confidence interval: 4.3-5.1) per week. These numbers are ∼4 times higher than the number of bowel movements produced by plecanatide. The change in the frequency of SBMs and CSBMs for other drugs, such as sodium picosulfate, velusetrag, linaclotide, elobixibat, lubiprostone, and prucalopride, was similar. The highest increases in the frequency of SBM and CSBM were 2.5 to 4 and 1 to 2.1 per week, respectively. Bisacodyl had the most noticeable loss of efficacy between week 1 and week 4; it reduced the frequencies of SBMs and CSBMs by 2.3 and 2.2, respectively. By contrast, the changes in the frequencies of SBMs and CSBMs were not as great with other drugs.
The data provided in this study may be a valuable supplement to the medication guidelines for the treatment of chronic constipation.
In this study, we used a model-based meta-analysis to quantitatively estimate the deviations from the baseline number of spontaneous bowel movements (SBMs) and complete spontaneous bowel movements (CSBMs) associated with pharmacotherapy for chronic constipation to bridge the knowledge gap in the guidelines for current medications.
A comprehensive survey was conducted using literature databases. In this study, we also included randomized placebo-controlled trials on chronic constipation. Pharmacodynamic models were established to describe the time course of the numbers of SBMs and CSBMs produced by each drug.
Data from 20 studies (comprising 9998 participants and 8 drugs) were used to build this model. The results showed that bisacodyl had the greatest effect on increasing the frequency of bowel movements, whereas plecanatide yielded the lowest increase in the number of SBMs and CSBMs. After eliminating the placebo effect, the maximal increase in bowel movement frequency associated with bisacodyl was 6.8 for SBMs (95% confidence interval: 6.1-7.6) and 4.7 for CSBMs (95% confidence interval: 4.3-5.1) per week. These numbers are ∼4 times higher than the number of bowel movements produced by plecanatide. The change in the frequency of SBMs and CSBMs for other drugs, such as sodium picosulfate, velusetrag, linaclotide, elobixibat, lubiprostone, and prucalopride, was similar. The highest increases in the frequency of SBM and CSBM were 2.5 to 4 and 1 to 2.1 per week, respectively. Bisacodyl had the most noticeable loss of efficacy between week 1 and week 4; it reduced the frequencies of SBMs and CSBMs by 2.3 and 2.2, respectively. By contrast, the changes in the frequencies of SBMs and CSBMs were not as great with other drugs.
The data provided in this study may be a valuable supplement to the medication guidelines for the treatment of chronic constipation.
摘要：
关于目前治疗便秘的处方药的指南，定量信息很少。此外，这些指南没有反映每种药物引起的排便次数的差异.
在这项研究中,我们使用基于模型的荟萃分析,定量估计与药物治疗慢性便秘相关的自发性排便(SBMs)和完全自发性排便(CSBMs)基线数量的偏差,以弥补当前用药指南中的知识差距.
使用文献数据库进行了全面调查。在这项研究中,我们还纳入了慢性便秘的随机安慰剂对照试验.建立药效学模型来描述每种药物产生的SBM和CSBM的数量的时间过程。
来自20项研究（包括9998名参与者和8种药物）的数据用于构建该模型。结果显示比沙可啶对增加排便频率的作用最大,whereasplecanatideyieldthelowestincreaseinthenumberofSBMsandCSBMs.Aftereliminationtheplaceboeffect,与比沙可啶相关的排便频率每周最大增加:SMM为6.8(95%置信区间:6.1~7.6),CSBM为4.7(95%置信区间:4.3~5.1).这些数字比plecanatide产生的排便次数高出4倍。其他药物的SBM和CSBM频率的变化，如匹可硫酸钠，velusetrag,利那洛肽,Elobixibat,鲁比前列酮,还有普鲁卡必利,是相似的。SBM和CSBM频率的最高增幅为每周2.5至4和1至2.1,分别。Bisacodyl在第1周和第4周之间的功效损失最明显；它分别将SBMs和CSBMs的频率降低了2.3和2.2。相比之下,SBMs和CSBMs的频率变化与其他药物相比并不显著.
本研究提供的数据可能是治疗慢性便秘的药物指南的有价值的补充。
在这项研究中,我们使用基于模型的荟萃分析,定量估计与药物治疗慢性便秘相关的自发性排便(SBMs)和完全自发性排便(CSBMs)基线数量的偏差,以弥补当前用药指南中的知识差距.
使用文献数据库进行了全面调查。在这项研究中,我们还纳入了慢性便秘的随机安慰剂对照试验.建立药效学模型来描述每种药物产生的SBM和CSBM的数量的时间过程。
来自20项研究（包括9998名参与者和8种药物）的数据用于构建该模型。结果显示比沙可啶对增加排便频率的作用最大,whereasplecanatideyieldthelowestincreaseinthenumberofSBMsandCSBMs.Aftereliminationtheplaceboeffect,与比沙可啶相关的排便频率每周最大增加:SMM为6.8(95%置信区间:6.1~7.6),CSBM为4.7(95%置信区间:4.3~5.1).这些数字比plecanatide产生的排便次数高出4倍。其他药物的SBM和CSBM频率的变化，如匹可硫酸钠，velusetrag,利那洛肽,Elobixibat,鲁比前列酮,还有普鲁卡必利,是相似的。SBM和CSBM频率的最高增幅为每周2.5至4和1至2.1,分别。Bisacodyl在第1周和第4周之间的功效损失最明显；它分别将SBMs和CSBMs的频率降低了2.3和2.2。相比之下,SBMs和CSBMs的频率变化与其他药物相比并不显著.
本研究提供的数据可能是治疗慢性便秘的药物指南的有价值的补充。
