A compartmental model for the uptake of chlorphentermine in isolated perfused rat lung

Equilibrium binding studies in vitro have established that chlorphentermine (CP) can be accumulated in rat lung by both binding and partitioning. Kinetic analysis of CP uptake in the isolated organ assuming an exponential process also suggests two separate mechanisms, one being saturable binding or transport, and the other, non-saturable partitioning. The present study was concerned with an alternative compartmental representation of the uptake process, and the validity of conclusions based on an exponential model. A three compartment model was finally selected which explain ed the observed uptake over a wide range of CP perfusate concentrations (2.5 x 10(-7) - 2.5 x 10(-5) mol/L) to within experimental error; it consisted of a binding and partitioning compartment in addition to one associated with the vascular bed. At low perfusate concentrations (2.5 x 10(-7) mol/L) uptake was essentially due to binding, while at higher perfusate concentrations (2.5 x 10(-5) mol/L) most uptake was due to partitioning. The total number of kinetically estimated binding sites (0.109 mumol/g) was less than that found by equilibrium dialysis for lung homogenates in vitro (8.3 mumol/g), suggesting an accessibility limitation for binding sites in the isolated preparation receiving a brief (10 min) perfusion. The data also indicate that there are probably two classes of binding sites or regional concentration of CP in the lung. It is proposed that interpretation of exponential model parameters may be problematical.