Abstract
The contribution of N4-acetylsulfadimethoxine (N4-AcSDM), a major metabolite of sulfadimethoxine (SDM), to the serum protein binding and pharmacokinetic interactions between SDM and ketoprofen (KPF) was investigated in rabbits. When SDM and KPF were intravenously coadministered, KPF indirectly reduced the serum protein binding of SDM through the interaction of KPF with N4-AcSDM, and significantly increased the total body clearance (Cltot) and steady-state volume of distribution (Vdss) of SDM. In addition, the co-administration of N4-AcSDM was found to increase Cltot and Vdss of SDM. These results indicate that N4-AcSDM contributes substantially to the serum protein binding and pharmacokinetic interactions between SDM and KPF in rabbits.
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