Grunenthal GmbH, Aachen, Germany.
Curr Med Res Opin. 2008 Nov;24(11):3185-96. doi: 10.1185/03007990802448056. Epub 2008 Oct 15.
Tapentadol is a new, centrally acting analgesic with two mechanisms of action, combining μ-opioid agonism and norepinephrine reuptake inhibition in a single molecule. This study assessed tapentadol immediate release (IR) in patients with postsurgical orthopedic pain.
This randomized, double-blind, phase II study involved patients with moderate-to-severe pain after bunionectomy surgery (first metatarsal with osteotomy). Patients (N = 269) were randomly assigned to receive tapentadol IR 50 or 100 mg, oxycodone HCl IR 10 mg, or placebo; the study drug was taken every 4-6 h, over a 72-h period starting 1 day after surgery (Evaluation Day 2). The primary endpoint was the sum of pain intensity over 24 h (SPI-24) on the second day after randomization (Evaluation Day 3). Potential limitations of this study included the use of rescue medication and the fact that it was not powered to statistically compare between-group differences in tolerability measures.
Mean (standard deviation [SD]) SPI-24 values on Evaluation Day 3 were significantly lower for tapentadol IR (50 mg: 33.6 [19.7], p = 0.0133; 100 mg: 29.2 [15.2], p = 0.0001) and oxycodone HCl IR 10 mg (35.7 [17.2]; nominal p = 0.0365) compared with placebo (41.9 [17.7]). The most common treatment-emergent adverse events for all treatment groups were characteristic of drugs with μ-opioid agonist activity. While providing similar analgesic efficacy, tapentadol IR 50 mg was associated with lower rates of nausea (46.3% vs. 71.6% for oxycodone HCl IR 10 mg), dizziness (32.8% vs. 56.7%), vomiting (16.4% vs. 38.8%), and constipation (6.0% vs. 17.9%), and a similar rate of somnolence (28.4% vs. 26.9%) compared with oxycodone HCl IR 10 mg.
Tapentadol IR 50 and 100 mg and oxycodone HCl IR 10 mg were effective in this study for the relief of acute postoperative pain following bunionectomy. The study results suggest improved gastrointestinal tolerability of tapentadol IR 50 mg compared with oxycodone at a dose showing comparable efficacy.
盐酸他喷他多是一种新型中枢作用镇痛药，具有双重作用机制，将μ阿片受体激动剂和去甲肾上腺素再摄取抑制剂结合在一个分子中。本研究评估了盐酸他喷他多速释制剂用于治疗骨科手术后疼痛。
这是一项随机、双盲、Ⅱ期研究，纳入了接受拇囊炎切除术（第一跖骨切开术）后出现中度至重度疼痛的患者。患者（N=269）随机分为盐酸他喷他多速释制剂 50mg 或 100mg、盐酸羟考酮控释制剂 10mg 或安慰剂组；研究药物在术后 1 天（评估日 2）开始的 72 小时内每 4-6 小时服用一次。主要终点是随机分组后第 2 天（评估日 3）的 24 小时疼痛强度总和（SPI-24）。本研究的潜在局限性包括使用解救药物，以及不具备统计比较组间耐受性差异的能力。
评估日 3 时，盐酸他喷他多速释制剂（50mg：33.6[19.7]，p=0.0133；100mg：29.2[15.2]，p=0.0001）和盐酸羟考酮控释制剂 10mg（35.7[17.2]；名义 p=0.0365）的 SPI-24 均值（标准差[SD]）均显著低于安慰剂（41.9[17.7]）。所有治疗组中最常见的治疗期间出现的不良事件均与具有μ阿片受体激动剂活性的药物特征相符。盐酸他喷他多速释制剂 50mg 与盐酸羟考酮控释制剂 10mg 相比，提供了相似的镇痛疗效，但恶心（46.3% vs. 71.6%）、头晕（32.8% vs. 56.7%）、呕吐（16.4% vs. 38.8%）和便秘（6.0% vs. 17.9%）的发生率更低，而嗜睡发生率相似（28.4% vs. 26.9%）。
盐酸他喷他多速释制剂 50mg 和 100mg 以及盐酸羟考酮控释制剂 10mg 对拇囊炎切除术的急性术后疼痛缓解均有效。研究结果表明，与羟考酮相比，他喷他多速释制剂 50mg 的胃肠道耐受性更好，而在疗效相当的情况下，他喷他多的剂量更低。
