Enhanced covalent binding of tolmetin to proteins in humans after multiple dosing.
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.
Zia-Amirhosseini
P
P
Department of Pharmacy, University of California, San Francisco 94143-0446.
Ojingwa
J C
JC
Spahn-Langguth
H
H
McDonagh
A F
AF
Benet
L Z
LZ
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*
D001798:Blood Proteins; D014046:Tolmetin