Zuniga John R, Phillips Ceib L, Shugars Daniel, Lyon James A, Peroutka Stephen J, Swarbrick James, Bon Charles
Department of Oral and Maxillofacial Surgery, UNC School of Dentistry, Chapel Hill, NC 27599-7450, USA.
J Oral Maxillofac Surg. 2004 Jul;62(7):806-15. doi: 10.1016/j.joms.2003.12.019.
The purpose of this single-blind, placebo-controlled, 3-arm parallel, randomized study was to compare the analgesic efficacy and tolerability of a single dose of 100 mg diclofenac potassium (Cataflam; Novartis, Stein, Switzerland), 100 mg diclofenac sodium softgel, and placebo in patients experiencing moderate to severe postoperative pain after third molar extraction.
Seventy-five patients (67% female with a mean age of 23, age range 18 to 34.5 years) participated in the study following removal of at least 1 impacted mandibular third molar. Patients received a single dose of study medication when their postoperative pain reached a moderate or severe intensity. Analgesic efficacy measures included the time to meaningful pain relief measured using a stopwatch and time to rescue medication. Pain relief (PR) and Pain intensity (PI) ratings were recorded at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours postdosing. Summary analgesic measures, including Summed Pain Relief Score (TOTPAR) and Summed Pain Intensity Differences (SPID), were calculated from the 0.25- to 6-hour responses. The time between pain relief and rescue and a global evaluation for the effectiveness of the study medications were recorded at the end of the study. Seven scheduled blood samples were collected from each patient for determining plasma concentrations of diclofenac anion.
Both diclofenac sodium softgel and Cataflam were significantly more effective than placebo (P <.0001) for all summary analgesic measures. The average overall pain relief was substantially better from diclofenac sodium softgel than from Cataflam, but the difference was not statistically significant (P =.14). In patients taking diclofenac sodium softgel, 50% of the patients experienced a time to onset of analgesic activity within 18 minutes and the median analgesic duration was 5 hours (302 minutes). Fifty percent of the patients taking Cataflam had a time to onset of action within 38 minutes, and the median duration of analgesia was 4.5 hours (272 minutes). At the time of rescue drug administration or 6 hours, whichever was earlier, 72% of the patients given diclofenac sodium softgel rated the medication as a very good or excellent pain reliever, whereas only 45% of the patients taking Cataflam gave these ratings. No serious adverse events were observed in this study. The mean concentrations of diclofenac from the diclofenac sodium softgel formulation were significantly different from the Cataflam formulation. The mean C(max) for the softgel was almost twice that of Cataflam and C(max) was reached an hour earlier, on average.
More diclofenac anion was absorbed at a quicker rate using the formulation diclofenac sodium softgel 100 mg than Cataflam. The softgel provided a very rapid onset of analgesic activity, a prolonged analgesic duration, and an acceptable side-effect profile in the postoperative third molar surgery pain model. In an acute pain situation, the rapid absorption of nonsteroidal anti-inflammatory drugs from a formulation like the Softgel may positively affect the time of onset and duration of inflammatory pain compared with other commercially available nonsteroidal anti-inflammatory drug formulations.
本单盲、安慰剂对照、三臂平行随机研究旨在比较单剂量100毫克双氯芬酸钾（扶他林；诺华公司，瑞士斯坦因）、100毫克双氯芬酸钠软胶囊与安慰剂对拔除下颌第三磨牙后中度至重度术后疼痛患者的镇痛效果和耐受性。
75例患者（67%为女性，平均年龄23岁，年龄范围18至34.5岁）在拔除至少1颗下颌阻生第三磨牙后参与本研究。当患者术后疼痛达到中度或重度强度时，给予单剂量研究药物。镇痛效果测量指标包括使用秒表测量的达到有效疼痛缓解的时间以及使用解救药物的时间。在给药后0.25、0.5、0.75、1、1.5、2、3、4、5、6、8和24小时记录疼痛缓解（PR）和疼痛强度（PI）评分。从0.25至6小时的反应计算出包括总疼痛缓解评分（TOTPAR）和总疼痛强度差异（SPID）在内的综合镇痛测量指标。在研究结束时记录疼痛缓解与使用解救药物之间的时间以及对研究药物有效性的总体评估。从每位患者采集7份预定血样以测定双氯芬酸阴离子的血浆浓度。
对于所有综合镇痛测量指标，双氯芬酸钠软胶囊和扶他林均比安慰剂显著更有效（P <.0001）。双氯芬酸钠软胶囊的平均总体疼痛缓解明显优于扶他林，但差异无统计学意义（P =.14）。服用双氯芬酸钠软胶囊的患者中，50%在18分钟内出现镇痛活性起效时间，中位镇痛持续时间为5小时（302分钟）。服用扶他林的患者中，50%在38分钟内出现起效时间，中位镇痛持续时间为4.5小时（272分钟）。在使用解救药物时或6小时（以较早者为准），给予双氯芬酸钠软胶囊的患者中72%将药物评为非常好或优秀的止痛剂，而服用扶他林的患者中只有45%给出这些评分。本研究中未观察到严重不良事件。双氯芬酸钠软胶囊制剂的双氯芬酸平均浓度与扶他林制剂显著不同。软胶囊的平均C(max)几乎是扶他林的两倍，且平均提前1小时达到C(max)。
与扶他林相比，使用100毫克双氯芬酸钠软胶囊制剂能更快地吸收更多双氯芬酸阴离子。在术后第三磨牙手术疼痛模型中，软胶囊提供了非常快速的镇痛活性起效、延长的镇痛持续时间以及可接受的副作用谱。在急性疼痛情况下，与其他市售非甾体抗炎药制剂相比，像软胶囊这样的制剂中非甾体抗炎药的快速吸收可能对炎症性疼痛的起效时间和持续时间产生积极影响。
