Analysis of the contributions of permeability and flow of intercompartmental clearance

Recent pharmacokinetic studies indicate that both flow and permeability contribute to intercompartmental clearance. A previous analysis of flow and permeability components of transcapillary exchange has been adapted to a three-compartment model of PA and NAPA pharmacokinetics. Data from a study that simultaneously determined the pharmacokinetic parameters of these two compounds made it possible to estimate permeability coefficients for the fast equilibrating compartment averaging 3.32 liters/min for PA and 1.35 liters/min for NAPA, and for the slow equilibrating compartment averaging 2.05 liters/min for PA and 0.78 liters/min for NAPA. These results were then used to estimated flow-intercompartmental clearance relationships for PA and NAPA and to predict the extent of hemodynamic changes causing the slow intercompartmental clearance of NAPA to decrease by 77% during hemodialysis without an apparent alteration in fast intercompartmental clearance.