INFLUENCE OF SEVERITY OF CHRONIC INFLAMMATORY JOINT DISEASE ON THE PHARMACOKINETICS OF INDOMETHACIN AND ETODOLAC

The goal of this study was to look for correlations between the severi ty of chronic inflammatory joint disease and pharmacokinetic parameter s of nonsteroidal antiinflammatory drugs. Disease severity data (pain severity and magnitude of abnormalities in laboratory tests for inflam mation) and pharmacokinetic data (area under the curve in the morning (AUCm) and maximum plasma concentration (Cmax) were collected during a prospective, randomized, double-blind, parallel-group study. Two grou ps of nine and 11 patients, respectively, were given 300 mg etodolac b .i.d or 50 mg indomethacin b.i.d. by the oral route, for three days, a fter a 36-hour placebo washout. Univariate analyses demonstrated stati stically significant negative correlations between pharmacokinetic par ameters of both study drugs and a number of disease severity parameter s. In the multivariate analysis of data for etodolac, the sigma erythr ocyte sedimentation rate contributed significantly to variations in al l pharmacokinetic parameters and explained 100% of the variations in f ree S-enantiomer AUCm and in total and free S-enantiomer Cmax. For ind omethacin, pain contributed to variations in Cmax values of the total and free forms; the sigma erythrocyte sedimentation rate was also a fa ctor in variations in total indomethacin. These negative correlations suggest that severity of chronic inflammatory joint disease may influe nce the pharmacokinetics of nonsteroidal antiinflammatory drugs.