Applecation of a Non-linear Dispersion Model to Analysis of the Renal Handling of p-Aminohippurate in Isolated Perfused Rat Kidney

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To analyze the renal handing of therapeutic compounds observed as a non-linear process with a diffusion phenomenon, we employed a non-linear dispersion model described with a partial differential equation and solved it by using the finite difference method with an implicit scheme in a model dependent analysis. In this study, the renal handing of p-aminohippurate (PAH) was investigated in isolated perfused rat kidney, in which a 50 μl bolus of injection solution containing [^3H]PAH and [^<14>C]inulin was administered rapidly into the renal artery. The venous outflows were then collected for 15 min with a fraction collector. The renal extraction ratio of PAH was decreased from 65% to 18% as the PAH concentration in the injection solution was increased from 2 μM to 10 mM. The PAH outrlow profile changed as the extraction process became saturated. With the non-linear dispersion model, the Michaelis-Menten parameters for the PAH extraction process were estimated by a model fitting calculation. The calculated values were 0.83 μmol/min/kidney for V_<max> and 89 μM for K_m. It was demonstrated that the model dependent analysis with a non-linear dispersion model is a useful approach to characterize renal drug handing, and is probably applicable for examining other non-linear processes which involve a diffusion phenomenon.
公益社団法人日本薬学会の論文
1999-06-15