Abstract
The pharmacokinetics of nadolol have been previously reported to be linear between single and steady-state dosing. Data from a study in our laboratory suggested greater than expected β-blockade with nadolol at steady state. Because the early potency studies were single-dose studies, we hypothesized there was a nonlinearity in nadolol pharmacokinetics which produced higher than expected plasma concentrations at steady state. Six normal volunteers from the previous study (steady state) volunteered to participate in the single-dose study. Plasma concentrations were determined for 24 hr following a single dose of nadolol, 80 mg. A simple, inexpensive, and accurate method for determination of nadolol in plasma or serum by HPLC with fluorometric detection is described. The AUCo–tau at steady state was greater than the AUC0–∞ following a single dose in five of the six subjects. The mean ratio of AUCss/AUCsd was 2.54. This value would be unity in the presence of linear pharmacokinetics. We conclude that the principle of superposition is not applicable for nadolol.
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REFERENCES
R. C. Heel, R. N. Brogden, G. E. Pakes, T. M. Speight, and G. S. Avery. Drugs 20:1–23 (1980).
J. Dreyfuss, R. A. Vukovich, J. M. Shaw, and D. A. Willard. J. Clin. Pharmacol. 17:300–307 (1977).
J. Dreyfuss, D. L. Griffith, S. M. Singhvi, J. M. Shaw, J. J. Ross, R. A. Vukovich, and D. A. Willard. J. Clin. Pharmacol. 19:712–720 (1979).
W. H. Frishman. Med. Clin. No. Am. 72:37–81 (1988).
R. A. Vukovich, J. E. Foley, B. Brown, D. A. Willard, M. Buckley, D. O'Kelly, D. Fitzgerald, W. Tormey, and A. Darragh. Br. J. Clin. Pharmacol. 7 (Suppl. 2):167S–172S (1979).
L. A. Inhen and J. P. Sall. In SAS User's Guide: Statistics, Version 5 Edition, SAS Institute, Cary, NC, 1985, pp. 656–664.
M. Gibaldi and D. Perrier (eds.). In Pharmacokinetics, 2nd ed. Marcel Dekker, New York, 1982, pp. 445–449.
C. M. Metzler, G. L. Elfring and A. J. McWren. Biometrics 30:562 (1974).
M. Gibaldi and D. Perrier (eds.). In Pharmacokinetics, 2nd ed., Marcel Dekker, New York, 1982, pp. 451–457.
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Krukemyer, J.J., Boudoulas, H., Binkley, P.F. et al. Comparison of Single-Dose and Steady-State Nadolol Plasma Concentrations. Pharm Res 7, 953–956 (1990). https://doi.org/10.1023/A:1015954108734
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DOI: https://doi.org/10.1023/A:1015954108734