The antiphlogistic,antinociceptive and antipyretic properties of fenclorac

Fenclorac (a,m-dichloro-p-cyclohexylphenylacetic acid, diethylammonium salt) is a potent nonsteroidal anti-inflammatory agent with significant analgesic and antipyretic activity. Fenclorac had an ED₅₀ of 7.9 mg/kg in the carrageenan paw edema assay and had a duration of action of 18–22 hours. Comparative tests in the carrageenan paw edema assay in the rat indicated that the potency of fenclorac was 13 times that of aspirin, 3.4 times phenylbutazone, 3 times ibuprofen and 0.3 times indomethacin. Fenclorac was less potent than indomethacin, but more potent than phenylbutazone or aspirin in treatment of developing or established adjuvant arthritis. The anti-inflammatory effectiveness of fenclorac did not depend upon the integrity of the adrenopituitary axis and was not affected by the route of administration or sex of the test animal. Fenclorac was 77 times more potent than aspirin and more than twice as potent as indomethacin in reducing fever in rats rendered hyperthermic with brewer's yeast. Fenclorac did not affect normal body temperatures. Fenclorac did not interfere with cellular immune mechanisms as measured by its lack of effectiveness in experimental allergic encephalomyelitis. Antinociceptive testing indicated that fenclorac had peripheral but not central analgesic activity. Fenclorac had an acute oral LD₅₀ in rats and mice of 285 and 430 mg/kg, respectively. The acute gastric lesion UD₅₀ for fenclorac was 7 mg/kg in the fasted rat. Studies using⁵¹Cr-tagged erythrocytes indicated that fenclorac did not produce significant fecal blood loss in the rat at twice the therapeutic ED₅₀ dose for up to 12 days after dosing. Extensive and prolonged fecal blood loss was observed with a corresponding dose of indomethacin for up to nine days after administration. Comparison of the antiinflammatory pharmacology, Therapeutic Ratio and the data obtained from the⁵¹Cr-fecal blood loss studies indicated that fenclorac was well tolerated after acute or subacute administration to the rat.