Relationship between the anti-inflammatory effects and intrapleural accumulations of anti-inflammatory drugs in rats carrageenin pleurisy.
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.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D002351:Carrageenan; D003907:Dexamethasone / Q000378:metabolism; D004840:Epirizole / Q000378:metabolism; D007660:Ketoprofen / Q000378:metabolism; D008297:Male; D010994:Pleura / Q000378:metabolism*; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D001798:Blood Proteins; D004840:Epirizole; D003907:Dexamethasone; D002351:Carrageenan; D007660:Ketoprofen