Interconversion Model Analysis for Acetohexamide and Its Metabolite, Hydroxyhexamide in the Rat by Application of the Simultaneous Multi-lines Fitting Technique

An interconversion model which incorporated a first-pass metabolism was applied to the disposition kinetics for acetohexamide and its reversible metabolite, hydroxyhexamide, in the rat. Four fundamental clearances, CL10, CL12, CL20 and CL21 were calculated from four area under the plasma concentration-time curve values. Simultaneous computer multi-lines fitting of the plasma concentration-time data and adequacy of pharmacokinetic parameters in this model were tested by using an iterative nonlinear least squares regression program, MULTI.