LINEAR AND NONLINEAR COMPETITION PLOTS IN THE DEOXYRIBOSE ASSAY FOR DETERMINATION OF RATE CONSTANTS FOR REACTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS WITH HYDROXYL RADICALS

Performing the deoxyribose (DR) assay for determination of the rate co nstants for reaction of non steroidal antiinflammatory drugs with hydr oxyl radicals led to some unusual competition plots. The molecules fro m the arylpropionic family of drugs: ibuprofen, flurbiprofen, ketoprof en and naproxen produced the linear relationship. However, acemetacin, diclofenac Na, flufenamic acid, indometacin, niflumic acid, tolmetin Na and sulindac presented non linear competition plots manifesting at relatively low drug concentrations. This effect was corrected by incre asing DR concentrations from 2.8 mM to 15 mM. The modification did not affect rate constants values for those derivatives which already pres ented a linear plot at 2.8 mM, but allowed to calculate rate constants for other compounds. It is suggested that the experimental conditions have to be adapted particularly for those derivatives with a relative ly high rate constant for reaction with the radical species. The oxica m derivatives (tenoxicam and piroxicam) presented another kind of devi ation that revealed a prooxidant effect in this system: non linear plo ts were also observed at relatively low drug concentrations, but in th e opposite direction than for the other molecules. This last effect wa s independent of DR concentration but could be corrected by increasing ascorbate concentration in the system.