Dietrich Thomas, Leeson Rachel, Gugliotta Barbara, Petersen Birte
The School of Dentistry, University of Birmingham, Birmingham, U.K.
Pain Pract. 2014 Apr;14(4):315-23. doi: 10.1111/papr.12082. Epub 2013 May 22.
Diclofenac is an effective and well-tolerated nonsteroidal anti-inflammatory drug (NSAID) frequently used in the treatment of acute pain. Marketed formulations for parenteral administration usually contain 75 mg/3 mL of diclofenac sodium, which provide limited dosing flexibility, and are usually given intramuscularly.
We present a randomized, double-blind, active comparator- and placebo-controlled, parallel-group phase III multicenter study, investigating efficacy and tolerability of a new 1 mL-volume formulation of diclofenac sodium (25, 50 or 75 mg) containing hydroxypropyl-β-cyclodextrin (HPβCD) as a solubility enhancer. This low-volume formulation allows subcutaneous (SC), in addition to intramuscular (IM) administration. Patients developing moderate-to-severe pain (≥ 50 mm on Visual Analogue Scale) after third molar extraction under local anesthesia were randomized to one of the 4 SC injections: 25 mg diclofenac HPβCD (n = 77), 50 mg diclofenac HPβCD (n = 76), 75 mg diclofenac HPβCD (n = 78), or placebo (n = 75).
Mean pain intensity difference at 1.5 hours postdose (primary endpoint) was higher in all diclofenac-treated groups than placebo group. The adjusted means (95% CI) were 36.5 (31.7 to 41.2) in diclofenac 25 mg group, 37.3 (32.6 to 42.1) in diclofenac 50 mg group, 37.7 (33.0 to 42.4) in diclofenac 75 mg group, and 12.3 (7.44 to 17.1) in placebo group. Both 25 and 50 mg doses of diclofenac produced significantly greater pain relief than placebo (P < 0.001 in both comparisons).
Single SC doses of diclofenac HPβCD of 25 and 50 mg are effective and well tolerated for relieving pain compared with placebo.
双氯芬酸是一种有效且耐受性良好的非甾体抗炎药（NSAID），常用于治疗急性疼痛。肠胃外给药的市售制剂通常含有75mg/3mL双氯芬酸钠，其给药灵活性有限，且通常为肌内注射。
我们开展了一项随机、双盲、活性对照和安慰剂对照的平行组III期多中心研究，调查一种新的1mL剂型的双氯芬酸钠（25、50或75mg）的疗效和耐受性，该剂型含有羟丙基-β-环糊精（HPβCD）作为增溶剂。这种小体积剂型除了可肌内注射外，还可皮下注射。在局部麻醉下拔除第三磨牙后出现中度至重度疼痛（视觉模拟量表评分≥50mm）的患者被随机分为4种皮下注射之一：25mg双氯芬酸HPβCD（n = 77）、50mg双氯芬酸HPβCD（n = 76）、75mg双氯芬酸HPβCD（n = 78）或安慰剂（n = 75）。
给药后1.5小时的平均疼痛强度差异（主要终点）在所有双氯芬酸治疗组中均高于安慰剂组。双氯芬酸25mg组的校正均值（95%CI）为36.5（31.7至41.2），双氯芬酸50mg组为37.3（32.6至42.1），双氯芬酸75mg组为37.7（33.0至42.4），安慰剂组为12.3（7.44至17.1）。25mg和50mg剂量的双氯芬酸产生的疼痛缓解均明显优于安慰剂（两项比较P均<0.001）。
与安慰剂相比，25mg和50mg单剂量皮下注射双氯芬酸HPβCD在缓解疼痛方面有效且耐受性良好。
