Kinetics of zomepirac, an oral, nonnarcotic analgesic, were studied in healthy males in 3 clinical experiments. In study A, zomepirac 100 mg was taken as tablet, capsule, and solution. Bioavailability of zomepirac from the 3 dosage forms was much the same. Zomepirac absorption was rapid, peak plasma concentrations being reached within 1 to 1 hr. Plasma concentration profile could be described by the 2-compartmentoral absorption model with an absorption rate constant (Ka) of 7.66 hr-1 t 1/2 = 0.09 hr), a rapid disposition rate constant (alpha) of 0.75 hr-1 (t 1/2 = 0.94 hr), and a slow disposition rate constant (beta) of 0.16 hr-1 (t 1/2 = 4.3 hr). In study B, safety and acceptability were established with 100 mg 4 times a day for 14 days followed by 150 mg 4 times a day for 14 days. Zomepirac plasma levels indicated attainment of steady state within less than 3 days of treatment. There was little drug accumulation on the regimens studied. There was no change in plasma kinetics after 14 days on either regimen. In study C, dose/bioavailability response was followed at 50-, 100-, and 200-mg dose levels. There were linear correlations between dose and peak plasma concentration, area under the plasma concentration-time curve, and urinary excretion of intact and total (intact + glucuronide conjugate) zomepirac during the 12 hr following drug administration.