Pharmacokinetics of piroxicam,a new nonsteroidal anti-inflammatory agent,under fasting and postprandial states in man

The kinetic disposition of piroxicam, under evaluation in man as a new anti-inflammatory drug, was studied in human volunteers given a single oral dose after both overnight fasting and food. Total absorption was uninfluenced by food intake, although the data indicate that food causes some delay in attainment of peak serum levels. The halflife of drug in plasma in the fasting subjects (37.5±2.4hr) was similar in both the fasting state and after food, suggesting that once-daily dosing may be appropriate for maintaining therapeutic plasma levels. Mean pharmacokinetic parameters for both studies in the fasting state and after meals are volume of distribution divided by availability, 0.140 or 0.136 liter/kg; total plasma clearance divided by availability, 2.68 or 3.12 ml/hr/kg. Approximately 10% of a single dose of piroxicam was eliminated in the urine within 8 days after oral drug administration. Renal clearance of the drug (0.28±0.10 ml/hr/kg) was 10.4% or less of plasma clearance, suggesting that piroxicam is extensively metabolized. In this study one subject showed a reduction in white blood count on the sixteenth day after a 60-mg dose; however, hematology values evaluated in both intraand intersubject comparisons did not show any other differences in the present study.This work was supported in part by a grant from Japan Rheumatoid Foundation (JRP).