The in vivo stability of tolmetin—plasma protein adducts was characterized in six healthy human volunteers after a 400 mg single dose and after a multiple‐dose regimen of 400 mg tolmetin every 12 hours for 10 days. Although the mean ± SD maximum bound concentration was only 2.72 ± 0.98 ng drug/mg protein after a single dose, it was almost an order of magnitude higher after multiple dosing. The protein adduct exhibited an average half‐life of 4.8 ± 0.9 days in contrast to the much shorter 5‐hour half‐lives for tolmetin and its glucuronide.Clinical Pharmacology and Therapeutics(1994)55,21–27; doi:10.1