Blood Levels of Drug at the Equilibrium State after Multiple Dosing


THERE is ample evidence1–20 that when a fixed dose of drug is administered in a fixed multiple-dose regimen, the blood levels of drug eventually reach a steady state in which the blood level time curve during any dosage interval is the same as it is in the preceding and in the following dosage interval. One may define the equilibrium state as that in which input of drug to the ‘body’ is equal to output of drug from the ‘body’ in a given dosage interval. The same equilibrium state will be reached when the initial dose is higher than the maintenance dose3,4.

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  1. 1

    Stewart, J. D., Rourke, G. M., and Allen, J. G., J. Amer. Med. Assoc., 110, 1885 (1938).

  2. 2

    Boxer, G. E., Jelinek, V. C., Tompsett, R., and Du Bois, R., J. Pharm. Exp. Therap., 92, 226 (1948).

  3. 3

    De Jongh, S. E., and Wijnans, M., Acta Physiol. Pharmacol. Neerl., 1, 237 (1950).

  4. 4

    Van Gemert, A. G. M., and Duyff, J. W., Acta Physiol. Pharmacol. Neerl., 1, 256 (1950).

  5. 5

    Dost, F. H., Der Blütspiegel: Kinetik der Konzentrationsaublaufe in der Kreisslauffussigkeit (Georg Thieme, Leipzig, 1953).

  6. 6

    Burns, J. J., Rose, R. K., Chenkin, T., Goldman, A., Schulert, A., and Brodie, B. B., J. Pharm. Exp. Therap., 109, 346 (1953).

  7. 7

    Butler, T. C., Mahaffee, C., and Waddell, W. J., J. Pharm. Exp. Therap., 111, 425 (1954).

  8. 8

    Swintosky, J. V., Bondi, A., jun., and Robinson, M. J., J. Amer. Pharm. Assoc. Sci. Ed., 47, 753 (1958).

  9. 9

    Krüger-Thiemer, E., J. Amer. Pharm. Assoc. Sci. Ed., 49, 31 (1960).

  10. 10

    Krüger-Thiemer, E., Klin. Wochen., 38, 514 (1960).

  11. 11

    Bünger, P., Diller, W., Führ, J., and Krüger-Thiemer, E., Arzneim. Forsch., 11, 247 (1961).

  12. 12

    Krüger-Thiemer, E., and Bünger, P., Arzneim. Forsch., 11, 867 (1961).

  13. 13

    Krüger-Thiemer, E., Theorie de Wirking Bakteriostatischer Chemotherapeutica, pp. 317–400 (Jakresbericht Borstel, Göttingen, Heidelberg, 1961).

  14. 14

    Krüger-Thiemer, E., Klin. Wochen., 40, 153 (1962).

  15. 15

    Krüger-Thiemer, E., Sulfanilamide una Verwandte Chemotherapeutica. (Handbuch der Hunt - und Geschlectskrankheiten, Fünfter Band, Erster-Teil, Springer-Verlag, Berlin, Göttingen, Heidelberg, 1962).

  16. 16

    Schlender, B., and Krüger-Thiemer, E., Arzneim. Forsch., 12, 992 (1962).

  17. 17

    Sutherland, J. M., Antimicrobial Therapy of the Newborn Infant, presented at the 3rd Intern. Cong. Chemotherapy, Stuttgart, July 1963.

  18. 18

    Wiegand, R. G., Buddenhagen, J. D., and Endicott, J., J. Pharm. Sci., 52, 268 (1963).

  19. 19

    Wagner, J. G., and Alway, C. D., Nature, 201, 1101 (1964).

  20. 20

    Cummings, A. J., and Martin, B. K., Biochem. Pharm., 13, 767 (1964).

  21. 21

    Teorell, T., Arch. Intern. Pharmacodyn. Therap., 57, 205 (1937).

  22. 22

    Dominguez, R., and Pomerene, E., Proc. Soc. Exp. Biol. and Med., 60, 173 (1945).

  23. 23

    Sch¨ck, O., and Šmahel, O., Antibiotic Med. and Clin. Therapy, 5, 98 (1958).

  24. 24

    Tait, J. F., Tait, Sylvia, A. S., Little, B., and Laumas, K. R., J. Clin. Investigation, 40, 72 (1961).

  25. 25

    Wagner, J. G., and Nelson, E., J. Pharm. Sci., 52, 610 (1963).

  26. 26

    Absorption and Distribution of Drugs, edit. by Binns, T. B. (E. and S. Livingstone, Ltd., Edinburgh and London, 1964).

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WAGNER, J., NORTHAM, J., ALWAY, C. et al. Blood Levels of Drug at the Equilibrium State after Multiple Dosing. Nature 207, 1301–1302 (1965).

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