In Vivo and in Vitro Binding of (-)-Hydroxyhexamide, a Major Metabolite of Acetohexamide, to Rabbit Serum

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The in vivo and in vitro bindings of (-)-hydroxyhexamide, a major metabolite of acetohexamide, to rabbit serum were examined by using an ultrafiltration method. The in vivo serum protein binding of (-)-hydroxyhexamide was much lower than the in vitro serum protein binding. The in vitro serum protein binding of (-)-hydroxyhexamide was strongly displaced by the addition of acetohexamide. Furthermore, the in vitro serum protein binding of (-)-hydroxyhexamide in the presence of acetohexamide and (-)-hydroxyhexamide at the same concentrations as those found 1.0 h after acetohexamide administration was approximately similar to the in vivo serum protein binding of (-)-hydroxyhexamide. These results lead us to conclude that acetohexamide, the parent drug of (-)-hydroxyhexamide, plays an important role in the in vivo serum protein binding of (-)-hydroxyhexamide.
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