Christensen Kyle, Daniels Stephen, Bandy Donald, Ernst Cynthia C, Hamilton Douglas A, Mermelstein Fred H, Wang Jianyuan, Carr Daniel B
Premier Research Group, Austin, Texas, USA.
Anesth Prog. 2011 Summer;58(2):73-81. doi: 10.2344/0003-3006-58.2.73.
Dyloject is a novel formulation of diclofenac intended for intravenous (IV) administration. This formulation employs the solubilizing agent hydroxypropyl-β-cyclodextrin to permit bolus IV administration. The efficacy and safety of 5 dose levels of IV diclofenac were compared with IV ketorolac and placebo following third molar extraction. This was a single-dose, randomized, double-blind, placebo- and comparator-controlled, parallel-group study. A total of 353 subjects with moderate to severe pain received placebo; ketorolac 30 mg; or IV diclofenac 3.75, 9.4, 18.75, 37.5, or 75 mg (N = 51 for all groups, except N = 47 for ketorolac). The primary endpoint was total pain relief over 6 hours (TOTPAR6) as measured by the visual analog scale (VAS). Secondary endpoints included multiple measures of pain intensity and relief; patient global evaluation; and times to pain relief and rescue medication. Dropouts and adverse effects (AEs) were also monitored. IV diclofenac was superior to placebo as measured by TOTPAR6 (P < .0001 for all doses except 3.75 mg, for which P = .0341). IV diclofenac 3.75 mg was statistically superior to placebo for TOTPAR2 and TOTPAR4. IV diclofenac at both 37.5 and 75 mg was superior to placebo (P < .05) at the earliest (5 minute) assessments of pain intensity and pain relief, but ketorolac was not. The proportion of patients reporting 30% or greater pain relief at 5 minutes was significantly greater after IV diclofenac 37.5 and 75 mg than after ketorolac 30 mg or placebo. Secondary endpoints confirmed the primary findings. Treatment-related AEs were generally mild to moderate and were typical for nonsteroidal anti-inflammatory drugs (NSAIDs). The more rapid onset of action of IV diclofenac compared with the reference injectable NSAID ketorolac suggests additional clinical benefit. If confirmed in larger series, these findings may improve the safety and efficacy of postoperative NSAID analgesia.
Dyloject是双氯芬酸的一种新型制剂，用于静脉注射（IV）。该制剂采用增溶剂羟丙基-β-环糊精，以允许大剂量静脉注射。在拔除第三磨牙后，将5种剂量水平的静脉注射双氯芬酸的疗效和安全性与静脉注射酮咯酸和安慰剂进行了比较。这是一项单剂量、随机、双盲、安慰剂和对照剂对照的平行组研究。共有353名中重度疼痛患者接受了安慰剂、30毫克酮咯酸或静脉注射双氯芬酸3.75、9.4、18.75、37.5或75毫克（除酮咯酸组为47人外，所有组均为51人）。主要终点是通过视觉模拟量表（VAS）测量的6小时内的总疼痛缓解（TOTPAR6）。次要终点包括疼痛强度和缓解的多项测量、患者整体评估以及疼痛缓解和急救药物的时间。还监测了退出情况和不良反应（AE）。通过TOTPAR6测量，静脉注射双氯芬酸优于安慰剂（除3.75毫克剂量外，所有剂量的P <.0001，该剂量的P = 0.0341）。静脉注射双氯芬酸3.75毫克在TOTPAR2和TOTPAR4方面在统计学上优于安慰剂。在最早（5分钟）的疼痛强度和疼痛缓解评估中，37.5毫克和75毫克的静脉注射双氯芬酸优于安慰剂（P <.05），但酮咯酸并非如此。在静脉注射双氯芬酸37.5毫克和75毫克后，报告在5分钟时疼痛缓解30%或更多的患者比例显著高于30毫克酮咯酸或安慰剂组。次要终点证实了主要发现。与治疗相关的AE通常为轻度至中度，是非甾体抗炎药（NSAID）的典型症状。与参考注射用NSAID酮咯酸相比，静脉注射双氯芬酸起效更快，提示有额外的临床益处。如果在更大规模的系列研究中得到证实，这些发现可能会提高术后NSAID镇痛的安全性和有效性。
