Enhanced covalent binding of tolmetin to proteins in humans after multiple dosing

Clin Pharmacol Ther. 1994 Jan;55(1):21-7. doi: 10.1038/clpt.1994.5.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blood Proteins / metabolism*
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Protein Binding
  • Tolmetin / administration & dosage
  • Tolmetin / metabolism*


  • Blood Proteins
  • Tolmetin