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.
Similar content being viewed by others
References
F. H. Dost.Der Blutspiegel, Thieme, Leipzig, 1953.
M. Gibaldi and D. Perrier.Pharmacokinetics, Dekker, New York, 1975.
R. E. Notari.Biopharmaceutics and Pharmacokinetics, 2nd ed., Dekker, New York, 1975.
J. M. van Rossum. Significance of pharmacokinetics for drug design and the planning of dosage regimens. In E. J. Ariëns (ed.),Drug Design, Vol. I, Academic Press, New York, 1971, pp. 469–521.
B. Beermann, K. Hellström, B. Lindström, and A. Rosen. Binding-site interaction of chlorthalidone and acetazolamide, two drugs transported by red blood cells.Clin. Pharmacol. Ther. 17:424–432 (1975).
H. L. J. Fleuren and J. M. van Rossum. Pharmacokinetics of chlorthalidone in man.Pharm. Wkbl. 110:1262–1264 (1975).
P. Collste, M. Garle, M. D. Rawlins, and F. Sjöqvist. Interindividual differences in chlorthalidone concentration in plasma and red cells of man after single and multiple doses.Eur. J, Pharmacol. 9:319–325 (1976).
D. Dieterle, J. Wagner, and J. W. Faigle. Binding of chlorthalidone (HygrotonR) to blood components in man.Eur. J. Clin. Pharmacol. 10:37–42 (1976).
H. L. J. Fleuren and J. M. van Rossum. Determination of chlorthalidone in plasma, urine and red blood cells by gaschromatography with nitrogen detection. Submitted (1977).
K. Diem and C. Lentner.Wissenschaftliche Tabellen, 7th ed., J. R. Geigy S.A., Basel, 1968, pp. 550–552.
J. C. Wagner.Biopharmaceutics and Relevant Pharmacokinetics, Drug Intelligence Publications, Hamilton Ill., 1971, pp. 302–317.
G. Beisenherz, F. W. Koss, L. Klatt, and B. Binder. Distribution of radioactivity in the tissues and excretory products of rats and rabbits following administration of C14-Hygroton.Arch. Int. Pharmacodyn. 161:76–93 (1966).
Author information
Authors and Affiliations
Additional information
This work was supported in part by a grant from the Netherlands Foundation for Medical Research (FUNGO).
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01061696