Linear and non linear 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 constants for reaction of non steroidal antiinflammatory drugs with hydroxyl radicals led to some unusual competition plots. The molecules from the arylpropionic family of drugs: ibuprofen, flurbiprofen, ketoprofen and naproxen produced the linear relationship. However, acemetacin, diclofenac Na, flufenamic acid, indometacin, indometacin, niflumic acid, tolmetin Na and sulindac presented non linear competition plots manifesting at relatively low drug concentrations. This effect was corrected by increasing DR concentrations from 2.8 mM to 15 mM. The modification did not affect rate constants values for those derivatives which already presented 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 relatively high rate constant for reaction with the radical species. The oxicam derivatives (tenoxicam and piroxicam) presented another kind of deviation that revealed a prooxidant effect in this system: non linear plots were also observed at relatively low drug concentrations, but in the opposite direction than for the other molecules. This last effect was independent of DR concentration but could be corrected by increasing ascorbate concentration in the system.
Parij
N
N
Department of Pharmaceutical Organic Chemistry, Free University of Brussels, Belgium.
Nagy
A M
AM
Neve
J
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001667:Binding, Competitive; D003855:Deoxyribose / Q000737:chemistry*; D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D007700:Kinetics; D016014:Linear Models; D015233:Models, Statistical; D016877:Oxidants / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D016877:Oxidants; D017665:Hydroxyl Radical; D003855:Deoxyribose