EFFECTS OF LYSINE CLONIXINATE AND KETOROLAC TROMETHAMINE ON PROSTANOID RELEASE FROM VARIOUS RAT ORGANS INCUBATED EX-VIVO

The release of prostanoids from rat brain, gastric mucosa, lungs and k idneys incubated ex vivo has been investigated for up to 5 h after ora l administration of 10 mg / kg lysine clonixinate or 1 mg / kg ketorol ac tromethamine. Additionally, 60 min after drug administration, a tim e point of near-maximal inhibition of prostanoid release, the effects of 2.5, 10 and 30 mg / kg lysine clonixinate and of 0.0225, 0.15 and 1 mg / kg ketorolac tromethamine were compared. In all organs investiga ted both drugs inhibited fatty acid cyclooxygenase (COX) in a dose-dep endent manner, but ketorolac tromethamine was more potent and had a lo nger-lasting effect than lysine clonixinate. While the ID50 values for lysine clonixinate were in the same order of magnitude for all 4 orga ns investigated, ketorolac tromethamine exhibited some organ selectivi ty with a particularly high activity in the kidneys. This effect might be related to the renal toxicity of ketorolac tromethamine. On the ot her hand, the difference in potency was smallest in brain suggesting t hat inhibition of central prostanoid biosynthesis could contribute to the rapid and effective inhibition of pain by both drugs. IC50 values for inhibition of purified COX-1 and COX-2 in vitro were slightly lowe r for lysine clonixinate (2.4 and 24.6 mu g / ml, respectively) than f or ketorolac tromethamine (3.7 and 25.6 mu g / ml, respectively).