Iwamura S, Kambegawa A, Miyasaka K
J Pharmacobiodyn. 1984 Aug;7(8):517-26. doi: 10.1248/bpb1978.7.517.
We simultaneously determined the time course of the anti-exudative effects of three types of anti-inflammatory drug and their concentrations in serum and pleural exudate in carrageenin-induced pleurisy in rats. Dexamethasone (DM, steroidal anti-inflammatory drug, 0.1 mg/kg, p.o.) in spite of the gradual decline of DM concentration in the pleural exudate with time and its actual loss at 16 h after carrageenin, showed an anti-exudative effect throughout the period of testing after carrageenin which was more marked in the relatively late phase than in the relatively early phase. Mepirizole (MP, non-acidic, non-steroidal antiinflammatory drug, 100 mg/kg, p.o.) showed an anti-exudative effect only at 3 h after carrageenin and not thereafter, although MP concentration in exudate was the same between 3 and 6 h after carrageenin and then declined gradually. Ketoprofen (KP, acidic, non-steroidal anti-inflammatory drug, 1 mg/kg, p.o.) showed an anti-exudative effect for 6 h after carrageenin and not thereafter, while KP concentration in exudate reached the peak at 3 h after carrageenin and then declined with time. However, at the relatively late phase (10 h after carrageenin) the twice administration of KP resulted in an increase in its exudate concentration enough to show an anti-inflammatory effect, but did not result in any more anti-exudative effect than the single administration of KP. Therefore, these differences in the anti-exudative effects of three types of anti-inflammatory drug can not be explained by the change in their concentrations in the inflamed tissue, but may reflect the difference in their intrinsic anti-inflammatory activities. The anti-inflammatory drugs accumulated in the inflamed pleural cavity independently of their ability to bind to plasma proteins, because the ratio of concentrations of three types of drug in exudate to those in serum were similar in spite of marked differences in protein binding capacities among these drugs.
我们同时测定了三种抗炎药物在角叉菜胶诱导的大鼠胸膜炎中的抗渗出作用的时间进程及其在血清和胸腔渗出液中的浓度。地塞米松（DM，甾体抗炎药，0.1mg/kg，口服）尽管随着时间的推移胸腔渗出液中DM浓度逐渐下降，且在角叉菜胶注射后16小时实际已消失，但在角叉菜胶注射后的整个测试期间均显示出抗渗出作用，在相对较晚阶段比相对较早阶段更明显。美吡立唑（MP，非酸性、非甾体抗炎药，100mg/kg，口服）仅在角叉菜胶注射后3小时显示出抗渗出作用，之后则无，尽管角叉菜胶注射后3至6小时渗出液中MP浓度相同，随后逐渐下降。酮洛芬（KP，酸性、非甾体抗炎药，1mg/kg，口服）在角叉菜胶注射后6小时显示出抗渗出作用，之后则无，而渗出液中KP浓度在角叉菜胶注射后3小时达到峰值，随后随时间下降。然而，在相对较晚阶段（角叉菜胶注射后10小时），两次给予KP导致其渗出液浓度升高至足以显示抗炎作用，但并未比单次给予KP产生更多的抗渗出作用。因此，三种抗炎药物抗渗出作用的这些差异不能用其在炎症组织中浓度的变化来解释，而可能反映了它们内在抗炎活性的差异。抗炎药物在发炎的胸腔中蓄积，与它们与血浆蛋白结合的能力无关，因为尽管这些药物在蛋白结合能力上有显著差异，但三种药物在渗出液与血清中的浓度比相似。
