Benorylate interaction with indomethacin and phenylbutazone

The simlutaneous oral administration of benorylate (4-(acetamido) phenyl 2-acetoxybenzoate) with either indomethacin or phenylbutazone to rats suffering from Freund's adjuvant-induced arthritis leads to an anti-inflammatory effect which is significantly greater than the effect of the same drugs administered alone. Such an additive anti-inflammatory effect is not apparent when the metabolites of benorylate (paracetamol, acetylsalicylic acid) are administered with indomethacin or phenylbutazone. Paracetamol does not increase the anti-inflammatory effect of indomethacin or phenylbutazone and acetylsalicylic acid clearly antagonizes it. The molecule of benorylate itsel is therefore responsible for the additive anti-inflammatory effect. However, if antipyretic activity (yeast-induced hyperthermia) is examined instead of anti-inflammatory activity, the simultaneous oral administration of the different drugs always produces an additive effect. It is concluded that the antagonism between indomethacin or phenylbutazone and non-steroidal anti-inflammatory drugs other than benorylate is present at some receptors but not all. The clinical implications of the results are discussed.