Three-compartment pharmacokinetic models of radiotracers used in the GFR-determination -- estimation of their parameters using the time-concentration curves.

BACKGROUND: In GFR measurements with radiotracers, there is evidence that a two-compartment model is unable to describe the full plasma curve, including early time points, but analyses generally focus on two-compartment models. AIMS: To analyze both the mammillary and catenary three-compartment model and to determine empirical relations between model constants and the overall GFR and ECV (extra-cellular volume). MATERIAL AND METHODS: Mathematical analysis of the three-compartment model. Full-curve patient data from 32 adults and 7 children were used to relate model parameters to GFR and ECV. RESULTS: Model volumes were found to be roughly proportional to ECV. In both models, the central (plasma) volume was V₁ = 0.24 x ECV and elimination rate from V₁ was k₁₀ = 4.2 x GFR/ECV. In the mammillary model, the two parallel volumes were V₂ = 0.28 x ECV, V₃ = 0.48 x ECV, and intercompartmental clearances were Cl₁₂ [mL/min] = 0.0058 x ECV [mL], Cl₁₃ = 0.042 x ECV. In the catenary model, the serial volumes were V₂ = 0.60 x ECV, V₃ = 0.16 x ECV, with clearances Cl₁₂ = 0.048 x ECV, Cl₂₃ = 0.0036 x ECV. CONCLUSION: Insight into the three-compartment model was achieved, and empirical relations to ECV and GFR/ECV were determined. [ABSTRACT FROM AUTHOR]