PHARMACOKINETIC-PHARMACODYNAMIC RELATIONSHIPS OF BROMFENAC IN MICE AND HUMANS

The relationship between pharmacodynamic effect and plasma concentrati ons of the analgesic bromfenac was assessed retrospectively. The drug was administered in single doses of 5, 10, 25, 50, or 100 mg to patien ts with oral surgery pain. Concentration-effect curves were generated by a semiparametric pharmacokinetic-pharmacodynamic procedure. The bro mfenac EC(50) (the effect site concentration giving 50% of the maximum effect) was estimated to be 0.36 mu g/ml in patients when all five do se groups were combined, and an E(max) model was used for pharmacodyna mic response. A similar EC(50) value, 0.40 pg/ml, was obtained when br omfenac was tested in a mouse pain model. On the basis of combined-dos e data, effect site concentrations were predicted to be above the anal gesic EC(50) for approximately 7-8 hours after a 50-mg bromfenac dose was taken in the fasting state. Predictions based on a pharmacokinetic -pharmacodynamic modeling procedure were ill reasonable agreement with the clinical observations.