Abstract
1. Dosing rat with suprofen produces suprofen equivalents that are covalently bound to plasma and tissue proteins in vivo.
2. Suprofen acyl glucuronide is reactive in vitro, resulting in suprofen equivalents covalently bound to proteins of plasma and tissues in a time-dependent manner.
3. Bile duct ligation of rat increases exposure to suprofen acyl glucuronide in vivo, which leads to enhanced covalent binding of suprofen equivalents to plasma proteins and to kidney tissue.
4. Covalent binding of suprofen equivalents to kidney tissue correlates with excretion of suprofen and suprofen glucuronide by the kidney.