酮洛芬药理研究进展

Progresses in Pharmacological Study of Ketoprofen

酮洛芬是2-芳基丙酸类非甾体抗炎药,主要通过抑制环氧合酶(COXs)、促炎肽和/或脂氧化酶(LOXs)的活性,从而抑制致炎性物质前列腺素(PGs)、白三烯(LTs)及血栓素的生物合成,使缓激肽释放减少,产生显著的解热、镇痛和抗炎作用。酮洛芬抗血小板聚集活性定量地取决于药物的酸性,对白细胞介素-8(IL-8)诱导的嗜中性粒细胞的趋化性具有选择性抑制作用,能增强其抗炎活性。酮洛芬的抗炎活性可能还与各种活化剂所引发的清除活性氧(ROS)、活性氮(RNS)及抑制中性粒细胞的呼吸突变的能力有关。酮洛芬因抑制COX-2活性而降低内源性PGF2α浓度,有诱导癫痫发作的潜在风险。局部用酮洛芬,可因为Ⅰ型游离自由基的作用而引起光敏毒副反应,还可因分子结构中分离的羧基而导致接触性皮炎反应。该文系统地综述近年来酮洛芬的药动学、药效学和药理毒理研究进展,重点从化学本质上揭示其产生药理、药效和毒副作用的分子机制,为设计、开发酮洛芬类新产品和临床合理用药提供参考。

Ketoprofen is a good 2- arylpropionic acid non- steroidal anti- inflammatory drug（ NSAID）. It performs it’s significant activities on antipyretic,analgesic and anti- inflammatory by inhibiting the enzyme activities of cyclooxygenases（ COXs）, proinflammatory peptides and / or lipoxygenases（ LOXs）, further inhibiting the biosynthesis of those inflammatory substances such as prostaglandins（ PGs）,bradykinins, leukotrienes（ LTs） and thromboxanes（ TXs）. The antiplatelet aggregation activity of ketoprofen quantitatively depends on the acidity. Its anti- inflammatory activity,which is strengthened by selectively inhibiting neutrophil chemotaxis induced by the interleukin- 8（ IL- 8）, may be partly due to the abilities to scavenge reactive oxygen species（ ROS） and reactive nitrogen species（ RNS）, as well as the abilities to inhibit the respiratory burst of neutrophils triggered by various activating agents. Because of unselectively inhibiting COX- 1 and COX- 2,ketoprofen may prevent the biosynthesis of prostaglandin E2（ PGE2） in gastric mucosal and further produce gastrotoxic activity,cause gastric mucosa damage or bleeding. Moreover,by inhibiting the COX- 2 activity,ketoprofen reduce the concentration of endogenous PGF2α, and this may increase the potential risk of seizures. Local usage of ketoprofen may produce photosensitive toxic side effects caused by type Ⅰ free radical reaction and contact dermatitis caused by the carboxyl group（- COOH） separated from the aromatic structure. In general, this paper systematically summarizes the progresses in pharmacological study of Ketoprofen, reveals its molecular mechanism of pharmacology,and illustrates the efficacy and side effects from its chemical structure nature. This paper may be helpful for the design and development of new products of ketoprofen class and the rational clinical use.