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The Impact of Lag Time on the Estimation of Pharmacokinetic Parameters. I. One-Compartment Open Model

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Abstract

Lag time in pharmacokinetics corresponds to the finite time taken for a drug to appear in systemic circulation following extravascular administration. Lag time is a reflection of the processes associated with the absorption phase such as drug dissolution and/or release from the delivery system and drug migration to the absorbing surface. Failure to specify the lag time can lead to inappropriate or erroneous estimates of pharmacokinetic parameters. This has been demonstrated in the case of a one-compartment open model by the pharmacokinetic analysis of bioequivalence data from a study involving the administration of propoxyphene napsylate to human volunteers. Subsequently, pharmacokinetic and statistical analyses of data obtained from a series of 49 simulations involving a wide range of absorption and elimination rate constants (0.05 to 5.00 and 0.01 to 0.95 hr−1, respectively) showed that lag time has a substantial effect on several primary and secondary pharmacokinetic parameters.

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REFERENCES

  1. M. Gibaldi and D. Perrier. Pharmacokinetics, Marcel Dekker, New York, 1982, pp. 409–416.

    Google Scholar 

  2. M. Bialer. A simple method for determining whether absorption and elimination rate constants are equal in the one-compartment open model with first-order processes. J. Pharmacokinet. Biopharm. 8(1):111–113 (1980).

    Google Scholar 

  3. K. K. H. Chan and K. W. Miller. Nonlinear regression approach for determining whether absorption and elimination rate constants are equal in the one-compartment open model with first-order processes. J. Pharm. Sci. 72(5):574–576 (1983).

    Google Scholar 

  4. I. H. Patel. Concentration ratio method to determine the rate constant for the special case when Ka = Ke. J. Pharm. Sci. 73(6):859–861 (1984).

    Google Scholar 

  5. P. E. Macheras. Graphical approach for determining whether absorption and elimination rate constants are equal in the one-compartment open model with first order processes. J. Pharm. Sci. 74(5):582–584 (1985).

    Google Scholar 

  6. P. E. Macheras. Developments in the concentration ratio method. J. Pharm. Sci. 74(9):1021 (1985).

    Google Scholar 

  7. H. P. Wijnand. Pharmacokinetic model equations for the one-and two-compartment models with first-order processes in which the absorption and exponential elimination or distribution rate constants are equal. J. Pharmacokin. Biopharm. 16(1):109–128 (1988).

    Google Scholar 

  8. J. Zhi. Unique pharmacokinetic characteristics of the one-compartment first-order absorption model with equal absorption and elimination rate constants. J. Pharm. Sci. 79(7):652–654 (1990).

    Google Scholar 

  9. J. G. Wagner. Pharmacokinetics, J. M. Richards Laboratory, Grosse Point Park, MI, 1969, pp. 83–84.

    Google Scholar 

  10. M. Rowland. Effects of some physiologic factors on bioavailability of oral dosage forms. In J. Swarbrick (ed.), Current Concepts in the Pharmaceutical Sciences: Dosage Form Design and Bioavailability, Lea & Febiger, Philadelphia, PA, 1973, pp. 190–191.

    Google Scholar 

  11. M. Rowland and T. N. Tozer. Clinical Pharmacokinetics: Concepts and Applications, Lea and Febiger, Philadelphia, 1989, p. 36.

    Google Scholar 

  12. J. Wagner. Fundamentals of Clinical Pharmacokinetics, Drug Intelligence, Hamilton, IL, 1975, pp. 81–82.

    Google Scholar 

  13. R. E. Notari. Biopharmaceutics and Clinical Pharmacokinetics: An Introduction, Marcel Dekker, New York, 1987, p. 122.

    Google Scholar 

  14. L. Shargel and A. B. C. Yu. Applied Biopharmaceutics and Pharmacokinetics, Appleton-Century-Crofts, Norwalk, CT, 1989, pp. 111–112.

    Google Scholar 

  15. W. A. Ritschel. Handbook of Basic Pharmacokinetics, Drug Intelligence, Hamilton, IL, 1986, pp. 10, 454–456.

    Google Scholar 

  16. P. G. Welling and F. L. S. Tse. Pharmacokinetics: Regulatory, Industrial, Academic Perspectives, Marcel Dekker, New York, 1988.

    Google Scholar 

  17. M. Gibaldi. Biopharmaceutics and Clinical Pharmacokinetics, Lea and Febiger, Philadelphia, 1991.

    Google Scholar 

  18. J. G. Wagner. Biopharmaceutics and Relevant Pharmacokinetics, Drug Intelligence, Hamilton, IL, 1971.

    Google Scholar 

  19. J. Swarbrick. Current Concepts in the Pharmaceutical Sciences: Biopharmaceutics, Lea and Febiger, Philadelphia, 1970.

    Google Scholar 

  20. J. P. Labaune. Handbook of Pharmacokinetics: Toxicity Assessment of Chemicals, Ellis Horwood, Chichester, England, 1989.

    Google Scholar 

  21. S. Niazi. Textbook of Biopharmaceutics and Clinical Pharmacokinetics, Appleton-Century-Crofts, New York, 1979.

    Google Scholar 

  22. R. A. Shipley and R. E. Clark. Tracer Methods for in Vivo Kinetics: Theory and Applications, Academic Press, New York, 1972.

    Google Scholar 

  23. B. N. LaDu, H. G. Mandel, and E. L. Way. Fundamentals of Drug Metabolism and Drug Disposition, Williams and Wilkins, Baltimore, MD, 1972.

    Google Scholar 

  24. A. Rescigno and G. Segre. Drug and Tracer Kinetics, Blaisdell, Waltham, MA, 1966.

    Google Scholar 

  25. D. R. Krishna and U. Klotz. Clinical Pharmacokinetics: A Short Introduction, Springer-Verlag, New York, 1990, pp. 101–149.

    Google Scholar 

  26. A. Akaike. Posterior probabilities for choosing a regression model. Ann. Inst. Math. Stat. 30(A):9–14 (1978).

    Google Scholar 

  27. G. Schwartz. Estimating the dimensionality of a model. Ann. Stat. 6(2):461–464 (1978).

    Google Scholar 

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Nerella, N.G., Block, L.H. & Noonan, P.K. The Impact of Lag Time on the Estimation of Pharmacokinetic Parameters. I. One-Compartment Open Model. Pharm Res 10, 1031–1036 (1993). https://doi.org/10.1023/A:1018970924508

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