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Nonlinear relationship between plasma and red blood cell pharmacokinetics of chlorthalidone in man

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Abstract

Plasma concentrations, red blood cell concentrations, and urinary excretion of chlorthalidone were measured after oral administration of single doses of 100 or 200 mg to ten human subjects. The decay of red blood cell concentrations showed a much longer elimination half-life than the terminal plasma decay curve. The in vitrodistribution of chlorthalidone between plasma and erythrocytes was similar to the in vivodistribution curve obtained from patients who were in a steady-state concentration range. A pharmacokinetic model was developed including nonlinear binding of chlorthalidone by the red blood cells, which in detail accounted for the observed time courses of drug in plasma and erythrocytes simultaneously.

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This work was supported in part by a grant from the Netherlands Foundation for Medical Research (FUNGO).

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Fleuren, H.L.J., van Rossum, J.M. Nonlinear relationship between plasma and red blood cell pharmacokinetics of chlorthalidone in man. Journal of Pharmacokinetics and Biopharmaceutics 5, 359–375 (1977). https://doi.org/10.1007/BF01061696

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  • DOI: https://doi.org/10.1007/BF01061696

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