Disposition and irreversible plasma protein binding of tolmetin in humans

Clin Pharmacol Ther. 1988 Jul;44(1):107-14. doi: 10.1038/clpt.1988.120.


The pharmacokinetics and irreversible plasma protein binding of tolmetin were studied in six healthy subjects after the administration of a single, 400 mg dose of tolmetin. With HPLC analysis, tolmetin, tolmetin glucuronide, and the isomers of tolmetin glucuronide, which result from intramolecular acyl migration in vivo, were detected in the plasma up to 4 hours after administration, whereas these conjugates were present in the urine up to 24 hours. Irreversible binding of tolmetin to plasma proteins occurred in all subjects. Irreversible binding exhibited a better correlation with exposure to tolmetin glucuronide (r = 0.5618) and the isomers of tolmetin glucuronide (r = 0.8200) than with exposure to tolmetin (-0.3635). This is consistent with the hypothesis that covalent binding occurs via the acyl glucuronide.

Publication types

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

MeSH terms

  • Adult
  • Biological Availability
  • Blood Proteins / metabolism*
  • Chromatography, High Pressure Liquid
  • Data Interpretation, Statistical
  • Female
  • Half-Life
  • Humans
  • Male
  • Pyrroles / pharmacokinetics*
  • Tolmetin / analogs & derivatives
  • Tolmetin / blood
  • Tolmetin / metabolism
  • Tolmetin / pharmacokinetics*
  • Tolmetin / urine


  • Blood Proteins
  • Pyrroles
  • 1-methyl-5-(4-carboxybenzoyl)-1H-pyrrole-2-acetic acid
  • tolmetin glucuronide
  • Tolmetin