EVANS BLUE-CARRAGEENAN PLEURAL EFFUSION AS A MODEL FOR THE ASSAY OF NONSTEROIDAL ANTIRHEUMATIC DRUGS

¹ Therapeutic Research Division, Miles Laboratories, Inc., Elkhart, Indiana

The addition of 0.025% carrageenan to intrapleural 0.075% Evans blue injections increased the effusive response. The amount of effusion varied from assay to assay; in 162 control groups (six rats/group) the estimated population mean volume of pleural fluid ± S.E. at six hours was 7.5 ± 0.07 ml. The reduction in the volume of pleural fluid elicited by the nonsteroidal antirheumatic drugs was dose related in contrast to the lack of consistent dose dependency when the dye alone was the pleural irritant. Relative potencies of the test compounds were determined in 2 by 3 assays with half-log dose increments, and the results were analyzed by factorial analyses. Their activities relative to phenylbutazone were: indomethacin, 26.9; flufenamic acid, 2.1; gold sodium thiomalate, 1.1; indoxole, 1.0; and acetylsalicylic acid, 0.3. With the exception of gold sodium thiomalate (i.m.), all compounds were administered p.o. Chloroquine phosphate and d-penicillamine failed to influence the effusive response. The resuits show that Evans blue-carrageenan-induced pleural effusion may be used to determine the relative potency of gold-and phenylbutazone-type antirheumatic compounds.