Ketorolac

376, 4

Male Wistar rats

Phase IV has been completed in the study of disposition of intravenous Ketorolac after cesarean section.

0.3-30 mg/kg

1.23 uM, 1.23 uM, 1.23 uM, 1.23 uM, 1.23 uM, 1.23 uM

(R, S)-Ketorolac is significantly more potent than indomethacin or diclofenac sodium in tests of acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema formation in rats, with ID50 of 0.24, 0.29 and 0.08 mg/kg, respectively. [1] Ketorolac produces significant inhibition of COX-1 activity and gastric PG synthesis with doses of >=1 mg/kg inhibiting COX-1 activity by 95% and gastric PG synthesis by >88%. Ketorolac does not significantly affect COX-2 activity at doses of <=3 mg/kg, but at doses of 10 and 30 mg/kg, Ketorolac produces significant inhibition of COX-2 activity by 75% and 91%, respectively. Ketorolac causes gastric damage in rats only at doses that inhibits both COX-1 and COX-2, or when given with a COX-2 inhibitor. [4]

Inhibition of Prostaglandin Formation, Recombinant COX-1 and COX-2 from rat (rCOX) and human (hCOX) expressed in a baculovirus system are purified and reconstituted with 2 mM phenol and 1 uM hematin. Then the cyclooxygenase activity is measured using a radiometric assay, and the specific activity of the final enzyme preparations used is between 20, 000 and 35, 000 units. Ketorolac (2 -15 uL) are diluted in DMSO and preincubated with the appropriate recombinant COX (3 -15 ng) at a final concentration of 0.01 to 1000 uM in a reaction mixture (150 uL) containing 50 mM Tris-HCl buffer (pH 7.9), 2 mM EDTA, 10% glycerol, 2 mM phenol, and 1 uM hematin for 10 minutes. The reaction is initiated by addition of [14C]arachidonic acid (50–60 mCi/mmol in a final concentration of 20 uM) and is terminated 45 seconds later by the addition of 100 uL of 0.2 N HCl and 750 uL of distilled water. The total reaction volume is then applied to a 1 mL C18 Sep-pak column that has previously been washed with 2 mL of methanol followed 5 mL of deionized water. Oxygenated products are eluted with 3 mL of a mixture of acetonitrile/water/acetic acid (50:50:0.1, v/v/v) and quantified by liquid scintillation spectroscopy.

DMSO 75 mg/mL, Water 75 mg/mL, Ethanol 75 mg/mL

Ketorolac is a COX-1 preferential inhibitor of the currently marked nonsteroidal anti-inflammatory drugs (NSAIDs).