Chellman G J, Lollini L O, Dorr A E, DePass L R
Department of Toxicology, Institute of Pathology, Toxicology and Metabolism, Syntex, Inc., Palo Alto, California 94303.
Hum Exp Toxicol. 1994 Feb;13(2):111-7. doi: 10.1177/096032719401300209.
The local tolerance of ketorolac tromethamine (Toradol, Syntex) was compared with that of four other injectable nonsteroidal anti-inflammatory drugs (NSAIDs) (diclofenac sodium, piroxicam, ketoprofen, and metamizol magnesium) in the rat paw-lick/muscle irritation assay as described previously. All drugs were tested at concentrations approved for clinical use. After subplantar (footpad) injection, ketorolac produced virtually no pain-on-injection as assessed by the number of paw-lick/lift responses during a 15 min observation period. The other NSAIDs produced slight to moderate paw-lick/lift responses. Redness and swelling at the injection site were less severe for ketorolac than for the other NSAIDs. After intramuscular (i.m.) injection, all of the NSAIDs produced some degree of muscle damage, as assessed histopathologically 24 h after injection. The lesions, consisting primarily of muscle degeneration, were less severe for ketorolac than for the other NSAIDs. Ketorolac and metamizol produced the smallest elevations in serum creatine kinase, as measured 2 h after i.m. dosing, not significantly different from isotonic saline. Overall, ketorolac was better tolerated in the assay than the other injectable NSAIDs, thereby suggesting the possibility of improved local tolerance on clinical use.
按照先前描述的方法，在大鼠舔爪/肌肉刺激试验中，将酮咯酸氨丁三醇（痛力克，先灵葆雅公司）与其他四种注射用非甾体抗炎药（NSAIDs）（双氯芬酸钠、吡罗昔康、酮洛芬和安乃近镁）的局部耐受性进行了比较。所有药物均以临床批准浓度进行测试。足底（脚垫）注射后，通过15分钟观察期内舔爪/抬脚反应的次数评估，酮咯酸注射时几乎不产生疼痛。其他NSAIDs产生轻微至中度的舔爪/抬脚反应。酮咯酸注射部位的发红和肿胀比其他NSAIDs轻。肌肉注射后，所有NSAIDs均产生一定程度的肌肉损伤，注射后24小时进行组织病理学评估。主要由肌肉变性组成的病变，酮咯酸比其他NSAIDs轻。肌肉注射给药2小时后测量，酮咯酸和安乃近引起的血清肌酸激酶升高最小，与等渗盐水无显著差异。总体而言，在该试验中酮咯酸的耐受性优于其他注射用NSAIDs，因此提示临床使用时局部耐受性可能有所改善。
