title: Enhanced covalent binding of tolmetin to proteins in humans after multiple dosing.
abstract: 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.
authors.affiliation: Department of Pharmacy, University of California, San Francisco 94143-0446.
authors.forename: P
authors.initials: P
authors.lastname: Zia-Amirhosseini
authors.forename: J C
authors.initials: JC
authors.lastname: Ojingwa
authors.forename: H
authors.initials: H
authors.lastname: Spahn-Langguth
authors.forename: A F
authors.initials: AF
authors.lastname: McDonagh
authors.forename: L Z
authors.initials: LZ
authors.lastname: Benet
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D011485:Protein Binding; D014046:Tolmetin / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D014046:Tolmetin