DISPOSITION AND REACTIVITY OF IBUPROFEN AND IBUFENAC ACYL GLUCURONIDES IN VIVO IN THE RHESUS MONKEY AND IN VITRO WITH HUMAN SERUM ALBUMIN

The disposition of ibuprofen and ibufenac, an analog of ibuprofen with a history of severe adverse reactions, was investigated in Rhesus monkeys after oral administration. Plasma concentrations of the parent drugs and their glucuronides were measured by a direct HPLC method. Ibuprofen and ibufenac were rapidly ab-sorbed and metabolized to their acyl glucuronides. The pharma-cokinetic parameters of ibuprofen and ibufenac exhibited notable interanimal variability. Ibufenac tended to have a higher area under the plasma concentration vs. time curve (AUC), and Its apparent clearance was lower. The plasma levels of acyl glucuronides were lower than parent drugs; the ratio of AUC in plasma for glucu-ronide/parent drug was 22.8 % and 10.5 % for ibuprofen and ibufe-nac, respectively. The degradation of ibufenac glucuronide in vitro was faster than ibuprofen glucuronide in aqueous buffer, human serum albumin, and human plasma solutions. Covalent binding o