ANTIINFLAMMATORY ACTIVITY OF INDOMETHACIN AND PLASMA CORTICOSTERONE IN RATS

¹ Merck Institute for Therapeutic Research, West Point, Pennsylvania; Rahway, New Jersey

The antiinflammatory activity of indomethacin was tested in intact and in adrenalectomized rats by determining the inhibition of edema induced in the paw by subplantar injection of carrageenan. Plasma corticosterone levels were determined in samples obtained immediately after foot volume measurements were made. Inhibition of edema by indomethacin was related to the log dose of the drug; it was identical in intact and in adrenalectomized rats even in the virtual absence of circulating corticosterone. When corticosterone was used as an antiinflammatory drug in adrenalectomized rats, its effectiveness was related to the log of plasma concentration. In dialysis experiments, indomethacin in plasma concentrations exceeding levels obtained with therapeutic doses did not affect plasma binding of corticosterone. It is concluded that the evidence does not support the concept that indomethacin produces antiinflammatory effects by adrenal stimulation or by effects on endogenous steroids.