Pharmacokinetics of Sustained-release Etodolac

Etodolac exhibits linear pharmacokinetics, good oral bioavailability, greater than 99% protein binding, a low oral clearance (almost exclusively non-renal), a relatively small volume of distribution and a half-life that averages 7.3 +/- 4.0 h. No significant pharmacokinetic differences have been noted in patients with mild to moderate renal impairment, in patients with cirrhosis, in the elderly or in patients with arthritis. The pharmacodynamics of the drug are well characterized in terms of pain intensity differences (PID) yielding an EC50 of 13 micrograms/ml. The extensive kinetic/dynamic characterization of etodolac, together with its short half-life, makes the drug an ideal candidate for a sustained-release (SR), once-a-day formulation. Etodolac SR formulations exhibit the same pharmacokinetic characteristics as the conventional-release (CR) formulation, except for a longer time to peak concentration and a lower peak concentration. Fluctuation ratios upon multiple dosing are comparable for equal total daily doses of etodolac SR and twice-daily doses of the CR formulation. Administration with food (high-fat meal) did not affect areas under the curve for either the CR or the SR product. Simulation analyses for etodolac SR suggest that PID responses are maintained over 24 h.