Zomepirac kinetics in healthy males

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 2 hr. Plasma concentration profile could be described by the 2‐compartment oral absorption model with an absorption rate constant (Ka) of 7.66 hr −1 (t½ = 0.09 hr), a rapid disposition rate constant (α) of 0.75 hr −1 (t½ = 0.94 hr), and a slow disposition rate constant (β) of 0.16 hr −1 (t½ = 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. Clinical Pharmacology and Therapeutics (1980) 27, 395–401; doi: 10.1038/clpt.1980.53