EVALUATION OF THE ANTIPYRETIC EFFECT OF KETOROLAC, ACETAMINOPHEN, ANDPLACEBO IN ENDOTOXIN-INDUCED FEVER

The authors studied the antipyretic effect of three intramuscular dose s of ketorolac (15, 30, and 60 mg), acetaminophen 650 mg PO, and place bo in healthy male volunteers using an endotoxin-induced fever model. In this double-blind, double-dummy, parallel study, subjects were assi gned randomly with equal probability to one of the above treatment gro ups. Thirty minutes after study medication administration, a 20 unit p er kilogram dose of reference standard endotoxin (RSE) was administere d intravenously, and temperature was determined every 15 minutes for a n 8-hour period. Compared with placebo, all active treatment groups de monstrated a statistically significant reduction in both adjusted area under the temperature-by-time curve (AAUC) and the maximum increase o ver baseline temperature (dTmax). Furthermore, the 30 mg intramuscular dose of ketorolac demonstrated approximately the same antipyretic act ivity os the 650 mg oral dose of acetaminophen, and there was a statis tically significant dose response across the three ketorolac doses stu died (P < .0001). The majority of side effects reported during this st udy were symptoms associated with fever, including chills, headache, m yalgia, and dizziness, all of which are effects of RSE. The frequency of side effects tended to be less in the treatment groups with the gre atest antipyretic activity.