EVALUATION OF KETOROLAC CONCENTRATIONS IN PLASMA AND GINGIVAL CREVICULAR FLUID FOLLOWING TOPICAL TREATMENT WITH ORAL RINSES AND DENTIFRICES

Two clinical studies were conducted to determine the relative amounts of ketorolac detectable locally in the gingival crevicular fluid (GCF) and systemically in plasma after oral, topical drug administration. T he rinse study compared topical administration of three concentrations of ketorolac iromethamine (0.1%, 0.05%, and 0.01%) in oral rinse form ulations administered topically and a perorally administered capsule ( 10 mg), and the dentifrice study compared two concentrations of ketoro lac in dentifrice formulations (0.15% and 1.0%) with a 0.1% oral rinse , all treatments administered topically. The dose-corrected systemic a vailability of the three oral rinses evaluated in the rinse study rela tive to the peroral capsule was about 15%, However, the ratios of the observed maximum GCF ketorolac concentration to maximum plasma ketorol ac concentration ranged from 22 to 49, compared to less than 1 for the peroral ketorolac capsule. Using this ratio as an estimate of the abi lity of a treatment to target the drug to the gingival tissue, these d ata indicate that the ketorolac oral rinses achieved greater delivery of drug to the gingival tissue (presumed site of action for periodonti tis) with a tourer systemic drug load than peroral administration of a ketorolac capsule. The dose-corrected relative systemic bioavailabili ties for the dentifrice treatments with respect to the 0.1% rinse in t he dentifrice study were 59.2% and 86.4% for the 1.0% and 0.15% dentif rices, respectively, indicating that significantly less ketorolac was systemically available from the two dentifrices relative to the oral r inse. The relative bioavailabilities of ketorolac in the GCF after dos ing with the dentifrice formulations with respect to the rinse were 89 .1% for the 1.0% dentifrice and 19.7% for the 0.15% dentifrice. Thus, the 1.0% dentifrice appears to provide statistically equivalent levels of ketorolac of the gingival tissue as the 0.1% oral rinse with signi ficantly less systemic exposure. The T-1/2 of ketorolac in the GCF was about 0.5 h for all three treatments, which is significantly less tha n the plasma half-life of about 5.3 h. These data suggest that GCF lev els of ketorolac should remain above the IC50 for PGE(2)-stimulated IL -1 bone resorption for about 7 h following treatment, assuming continu ation of the first-order elimination observed over the first two postd osing hours. We conclude that oral rinses and dentifrices are effectiv e and preferred Vehicles for administration of ketorolac for use in tr eatment of periodontitis.