THE INFLUENCE OF BROMFENAC ON THE PHARMACOKINETICS AND PHARMACODYNAMIC RESPONSES TO GLYBURIDE IN DIABETIC SUBJECTS

Study Objective. To assess the effect of bromfenac sodium, a nonnarcot ic analgesic drug under development, on the pharmacokinetics and pharm acodynamics of glyburide in patients with type II diabetes. Design. Ra ndomized, double-blind, placebo-controlled, multiple-dose study with a two-period crossover design. Patients. Eleven men and one woman (age 36-64 yrs) whose diabetes was responsive to oral sulfonylurea therapy. Interventions. Placebo or bromfenac 50 mg was given as a single oral dose 3 times/day for the first 3 days of the study. On days 4-6, patie nts received the alternative treatment. For at least 3 months before a nd during the study, patients took their usual single daily dose of gl yburide 10 mg. Measurements and Main Results. Bromfenac concentrations were measured by high-performance liquid chromatography with ultravio let detection. Glyburide concentrations were measured by gas chromatog raphy with nitrogen-phosphorus detection. Glycemia was measured repeat edly on day 3 of each treatment. Pharmacokinetic analysis was performe d with noncompartmental techniques. No significant differences in the pharmacokinetics of glyburide or in the pharmacodynamic response of se rum glucose levels were observed between placebo and bromfenac. Inters ubject variability of concentrations was modest for glyburide and gluc ose, with a CV of 43% or less. Conclusion. Glyburide levels are not ch anged during concomitant administration of bromfenac.