Skip to main content
SpringerLink
Log in

Mean Residence Time Concepts for Pharmacokinetic Systems with Nonlinear Drug Elimination Described by the Michaelis–Menten Equation

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Equations for the mean residence time (MRT) of drug in the body and related functions are derived for drugs which are intravenously administered into a one- or two-compartment system with Michaelis–Menten elimination. This MRT is a function of the steady-state volume of distribution and time-average clearance obtained from the dose and area under the curve (dose/AUC). The differences between the MRT calculated by the proposed method and by using the moment theory method (AUMC/AUC) are demonstrated both mathematically and by computer simulations. The validity of the proposed method for calculation of MRT and its relationship to the moment theory result have also been assessed by examining the percentage of the administered dose eliminated and the percentage of the total area attained at MRT and at AUMC/AUC in relation to the dose. The equations evolved should be helpful in clarifying residence time derivations and in defining the disposition characteristics and differences between linear and nonlinear systems. Direct methods are provided for calculation of Michaelis–Menten parameters based on the relationship between MRT and dose.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. K. Yamaoka, T. Nakagawa, and T. Uno. J. Pharmacokin. Biopharm. 6:547–558 (1978).

    Google Scholar 

  2. L. Z. Benet and R. L. Galeazzi. J. Pharm. Sci. 68:1071–1074 (1979).

    Google Scholar 

  3. S. Riegelman and P. Collier. J. Pharmacokin. Biopharm. 8:509–533 (1980).

    Google Scholar 

  4. A. Rescigno. J. Theor. Biol. 39:9–27 (1973).

    Google Scholar 

  5. W. R. Gillespie and P. Veng-Pedersen. J. Pharmacokin. Biopharm. 13:549–554 (1985).

    Google Scholar 

  6. W. J. Jusko. In W. E. Evans, J. J. Schentag, and W. J. Jusko (eds.), Applied Pharmacokinetics—Principles of Therapeutic Drug Monitoring, 1st ed., Applied Therapeutics, San Francisco, 1980, p. 662.

    Google Scholar 

  7. D. F. Smith. Expansion of First Moment Analysis in Pharmacokinetics, M.S. thesis, Ohio State University, Columbus, 1984.

  8. A. E. Staubus and D. F. Smith. In L. Z. Benet, G. Levy, and B. L. Ferraiolo (eds.) Pharmacokinetics—A Modern View, Plenum Press, New York, 1984, pp. 411–414.

    Google Scholar 

  9. J. G. Wagner. J. Pharmacokin. Biopharm. 1:103–121 (1973).

    Google Scholar 

  10. D. J. Cutler. Biopharm. Drug Disp. 8:87–97 (1987).

    Google Scholar 

  11. A. T. Chow and W. J. Jusko. Pharm. Res. 4:58–60 (1987).

    Google Scholar 

  12. M. L. Rocci and W. J. Jusko. Comp. Prog. Biomed. 16:203–216 (1983).

    Google Scholar 

  13. P. Veng-Pedersen and W. Gillespie. J. Pharm. Sci. 74:791–792 (1985).

    Google Scholar 

  14. L. Z. Benet. J. Pharmacokin. Biopharm. 13:555–558 (1985).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, Buffalo, New York, 14260

    Haiyung Cheng & William J. Jusko

  2. Department of Pharmacokinetics and Drug Metabolism, Merrell Dow Pharmaceuticals, Inc, Indianapolis, Indiana, 46268

    Haiyung Cheng

Authors
  1. Haiyung Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William J. Jusko
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheng, H., Jusko, W.J. Mean Residence Time Concepts for Pharmacokinetic Systems with Nonlinear Drug Elimination Described by the Michaelis–Menten Equation. Pharm Res 5, 156–164 (1988). https://doi.org/10.1023/A:1015960806202

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015960806202

Search

Navigation