An algorithm and computer program for calculating the mean transit time and distribution rate parameters of generated metabolites undergoing linear tissue distribution and linear or non-linear central elimination

A method is described for calculating the mean transit time and distribution rate parameters of a generated primary metabolite undergoing linear distribution and linear or non-linear central elimination, and of catenary metabolites with any precursor order. It is also applicable to a drug and its interconversion metabolite and does not require separate administration of the metabolite. The method allows steady-state volume of distribution and distribution clearance of a metabolite to be calculated, provided that the central volume of distribution of the metabolite is known. An algorithm and computer program to implement the proposed method are presented. The calculations require the plasma concentration versus time curves of the metabolite and its precursor. The method is applied to both published and simulated data.