Background

There is a clinical need for potent opioids that produce little or no respiratory depression. In the current study we compared the respiratory effects of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg.

Methods

Fifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized design. The main end-point of the study was the effect of treatment on the ventilatory response to hypercapnia and ventilation at an extrapolated end-tidal P_CO2 of 7.3 kPa (55 mmHg, VE55); VE55 was assessed prior and for 6-h following drug intake.

Results

All three treatments had typical opioid effects on the hypercapnic ventilatory response: a shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg had a significantly larger respiratory depressant effect than tapentadol 100 mg (mean difference −5.0 L min⁻¹, 95% confidence interval: −7.1 to −2.9 L min⁻¹, P<0.01), but not larger than tapentadol 150 mg (oxycodone vs. tapentadol 150 mg: P>0.05).

Conclusions

In this exploratory study we observed that both tapentadol and oxycodone produce respiratory depression. Tapentadol 100 mg but not 150 mg had a modest respiratory advantage over oxycodone 20 mg. Further studies are needed to explore how these results translate to the clinical setting.

中文翻译：

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比较他喷他多和羟考酮对健康志愿者的呼吸作用的实验研究

背景

临床上需要产生很少或没有呼吸抑制作用的有效的阿片类药物。在目前的研究中，我们比较了μ阿片受体激动剂和去甲肾上腺素再摄取抑制剂他喷他多和选择性μ阿片受体激动剂羟考酮的呼吸作用。我们假设他喷他多100毫克比羟考酮20毫克对呼吸控制的作用较小。

方法

15名健康志愿者被随机分配接受交叉双盲随机设计的口服他喷他多（100和150 mg），羟考酮20 mg或安慰剂即释片剂。该研究的主要终点是在潮气末P _{CO 2}推断为7.3 kPa（55 mmHg，VE55）时，治疗对高碳酸血症和通气的通气反应的影响。VE55在药物摄入之前和之后6小时进行评估。

结果

三种治疗对高碳酸血症通气反应均具有典型的阿片类药物作用：向右移动与反应斜率降低相关。羟考酮20毫克具有比他喷他多100mg的一个显著较大呼吸抑制剂效果（平均差异-5.0大号分钟^-1，95％置信区间：-7.1到-2.9大号分钟^-1，P <0.01），但不超过150他喷他多较大毫克（羟考酮与他喷他多150毫克：P > 0.05）。

结论

在这项探索性研究中，我们观察到他喷他多和羟考酮都可引起呼吸抑制。相对于羟考酮20毫克，他喷他多100毫克而非150毫克具有适度的呼吸优势。需要进一步研究以探索这些结果如何转化为临床环境。