RELATIONSHIP BETWEEN PHARMACOKINETICS AND THE ANALGESIC EFFECT OF KETOROLAC IN THE RAT

The relationship between the pharmacokinetic properties and the analge sic effect of ketorolac was evaluated with the pain-induced functional impairment model in the rat. Female Wistar rats were injected with ur ic acid in the knee of the right hind limb to produce dysfunction. The n, animals received an oral dose of 0.3, 1, 1.8, 3.2 or 5.6 mg/kg of k etorolac tromethamine and analgesic effect and blood concentration, de termined by high-performance liquid chromatography, were evaluated at selected times for a period of 4 hr. Ketorolac produced a dose-depende nt analgesic effect, measured as a recovery of the functionality of th e injured limb, which reached its maximal effect at doses of 3.2 mg/kg or higher. When functionality index was plotted against ketorolac blo od concentration, a direct relationship was observed that was well des cribed by the sigmoidal maximal effect model. The data strongly sugges t that ketorolac's analgesic effect depends on the blood concentration of the drug.