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 × ECV and elimination rate from V1 was k10 = 4.2 × GFR/ECV. In the mammillary model, the two parallel volumes were V2 = 0.28 × ECV, V3 = 0.48 × ECV, and intercompartmental clearances were Cl12 [mL/min] = 0.0058 × ECV [mL], Cl13 = 0.042 × ECV. In the catenary model, the serial volumes were V2 = 0.60 × ECV, V3 = 0.16 × ECV, with clearances Cl12 = 0.048 × ECV, Cl23 = 0.0036 × ECV.

CONCLUSION: Insight into the three-compartment model was achieved, and empirical relations to ECV and GFR/ECV were determined.