Profile of Etodolac: Pharmacokinetic Evaluation in Special Populations

The pharmacokinetics of etodolac, a new nonsteroidal anti-inflammatory drug, were compared in normal subjects, in patients with renal and hepatic disease, and in elderly patients. In 28 normal subjects, orally administered etodolac was rapidly absorbed. By 1.2 hours after ingestion of a 200 mg dose, the maximum serum concentration (Cmax) averaged 15.9 micrograms/ml, with more than 99% of the drug bound to serum protein. Clearance was primarily hepatic. The mean half-life (t1/2) was 6 to 7 hours. There were no apparent differences in Cmax, the time at which Cmax occurred (tmax), area under the serum concentration/time curve (AUC0-24), or t1/2 between groups of young men (n = 20), elderly men (n = 24), and elderly men with osteoarthritis (n = 20), after a single dose of etodolac or after 7 days of subchronic administration. Moreover there was no evidence of accumulation. There also were no differences in Cmax, tmax, AUC0-24 or t1/2 between groups of normal subjects (n = 10) and patients with mild-to-moderate renal impairment (n = 10). Patients with end-stage renal disease who were receiving chronic hemodialysis had the same mean serum concentration of free drug as normal subjects, even though mean serum levels of protein-bound etodolac were slightly lower than those in the normal subjects. The only significant (p less than 0.05) difference between patients with stable hepatic cirrhosis and normal, age-matched subjects was a slightly shorter tmax in the cirrhotic subjects (1.1 vs. 1.4 hours). These findings suggest that no alteration of etodolac dosage would be necessary in these high-risk groups.