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Pharmacokinetic profiles of canrenoic acid (CRA) and canrenone (CR), the reversible metabolite of CRA, were studied in the rat after intraportal (pv) administration in comparison with those after intravenous (iv) administration using an interconversion model. In the clearances for the irreversible loss. CL20 of CR was larger than CL10 of CRA. Nevertheless, the real plasma clearance of CR was less than that of CRA. The distribution volume V1 of CRA was almost close to the real distribution volume Vss.real.D of CRA at the steady state. The hepatic available fraction of CRA, FH1 and sequential hepatic available fraction of generated metabolite, FH2, were estimated. Simultaneous computer multi-line fitting of plasma concentration-time data was carried out and the adequacy of pharmacokinetic parameters in this model was tested using the iterative nonlinear least-squares regression program, MULTI.
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