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Analysis of the contributions of permeability and flow to intercompartmental clearance

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Abstract

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 estimate 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.

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This work was supported by grant GM-22371 from the National Institute of General Medical Sciences, National Institutes of Health, and by the Louise D. Roland Memorial Fund.

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Stec, G.P., Atkinson, A.J. Analysis of the contributions of permeability and flow to intercompartmental clearance. Journal of Pharmacokinetics and Biopharmaceutics 9, 167–180 (1981). https://doi.org/10.1007/BF01068080

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