Nonlinear relationship between plasma and red blood cell pharmacokinetics of chlorthalidone in man
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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.
Key wordschlorthalidone pharmacokinetics in man oral administration plasma concentrations red blood cell concentrations nonlinear distribution pharmacokinetic model
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- 1.F. H. Dost.Der Blutspiegel, Thieme, Leipzig, 1953.Google Scholar
- 2.M. Gibaldi and D. Perrier.Pharmacokinetics, Dekker, New York, 1975.Google Scholar
- 3.R. E. Notari.Biopharmaceutics and Pharmacokinetics, 2nd ed., Dekker, New York, 1975.Google Scholar
- 4.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.Google Scholar
- 6.H. L. J. Fleuren and J. M. van Rossum. Pharmacokinetics of chlorthalidone in man.Pharm. Wkbl. 110:1262–1264 (1975).Google Scholar
- 9.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).Google Scholar
- 10.K. Diem and C. Lentner.Wissenschaftliche Tabellen, 7th ed., J. R. Geigy S.A., Basel, 1968, pp. 550–552.Google Scholar
- 11.J. C. Wagner.Biopharmaceutics and Relevant Pharmacokinetics, Drug Intelligence Publications, Hamilton Ill., 1971, pp. 302–317.Google Scholar