COMPT, a time-sharing program for nonlinear regression analysis of compartmental models of drug distribution

  • Morris Pfeffer


COMPT, a computer program for optimizing the solution of integral compartmental models of drug distribution by nonlinear regression analysis, is written in extended BASIC for use in time-sharing computer systems. It is based on Hartley's modification of the Gauss-Newton gradient method. The characteristics and features of the program are indicated, and the program source listing is presented. This version of COMPT is designed to solve the two-compartment open model of intravenous drug administration. Examples of the results of the operational program are presented. The program is modifiable to permit analytical solutions for other types of systems described by nonlinear equations.

Key words

pharmacokinetics nonlinear regression drug distribution compartmental models computer program BASIC time sharing spectinomycin naloxone 


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  1. 1.
    J. G. Wagner.Pharmacokinetics, J. M. Richards Laboratory, Grosse Point Park, Mich., 1969.Google Scholar
  2. 2.
    H. D. Van Liew. Semilogarithmic plots of data which reflect a continuum of exponential processes.Science 138: 682–683 (1962).PubMedCrossRefGoogle Scholar
  3. 3.
    S. D. Foss. A method for obtaining initial estimates of the parameters in exponential curve fitting.Biometrics 25: 580–584 (1969).CrossRefGoogle Scholar
  4. 4.
    J. G. Wagner and J. I. Northam. Estimation of volume of distribution and half-life of a compound after rapid intravenous injection.J. Pharm. Sci. 56: 529–531 (1967).PubMedCrossRefGoogle Scholar
  5. 5.
    S. Riegelman, J. C. K. Loo, and M. Rowland. Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment.J. Pharm. Sci. 57: 117–123 (1968).PubMedCrossRefGoogle Scholar
  6. 6.
    K. B. Bischoff and R. L. Dedrick. Generalized solution to linear, two-compartment, open model for drug distribution.J. Theoret. Biol. 29: 63–83 (1970).CrossRefGoogle Scholar
  7. 7.
    W. H. Swann. A survey of non-linear optimization techniques.FEBS Letters Suppl. 2: S39-S55 (1969).CrossRefGoogle Scholar
  8. 8.
    W. Lowenthal and B. L. Vitsky. Computer program for a double exponential equation to determine biological constants.J. Pharm. Sci. 56: 169–173 (1967).PubMedCrossRefGoogle Scholar
  9. 9.
    F. W. Mueller and S. V. Lieberman. Fitting a double-exponential curve to observed salicylate concentrations in blood.J. Pharm. Sci. 59: 514–517 (1970).PubMedCrossRefGoogle Scholar
  10. 10.
    H. O. Hartley. The modified Gauss-Newton method for the fitting of non-linear regression functions by least squares.Technometrics 3: 269–280 (1961).CrossRefGoogle Scholar
  11. 11.
    E. Kruger-Thiemer and B. Schlender. Die Losung chemotherapeutischer Probleme durch programmgesteuerte Ziffernrechenautomaten. 2. Mitteilung: Die exakte Berechnung der Gleichungsparameter und ihrer Vertrauensgrenzen mit Hilfe des Gauss-Newton-Iterations-verfahrens.Arzneim.-Forsch. 13: 891–894 (1963).Google Scholar
  12. 12.
    E. Kruger-Thiemer. Die Losung chemotherapeutischer Probleme durch programm-gesteuerte Ziffernrechenautomaten. 4. Mitteilung: Das Gauss-Newton-Iterationsverfahren für vier Gleichungsparameter.Arzneim.-Forsch. 14: 1332–1334 (1964).Google Scholar
  13. 13.
    C. M. Metzler.A User's Manual for NONLIN, The Upjohn Co., Technical Report 7292/69/7292/005, Kalamazoo, Mich., 1969.Google Scholar
  14. 14.
    N. R. Draper and H. Smith.Applied Regression Analysis, 1st corrected printing, Wiley, New York, 1968.Google Scholar
  15. 15.
    V. F. Smolen. Quantitative determination of drug bioavailability and biokinetic behavior from pharmacological data for ophthalmic and oral administrations of a mydriatic drug.J. Pharm. Sci. 60: 354–365 (1971).PubMedCrossRefGoogle Scholar
  16. 16.
    G. J. Cooper. The numerical solution of stiff differential equations.FEBS Letters Suppl. 2: S22-S29 (1969).CrossRefGoogle Scholar
  17. 17.
    S. A. Kaplan, M. Lewis, M. A. Schwartz, E. Postma, S. Cotler, C. W. Abruzzo, T. L. Lee, and R. E. Weinfeld. Pharmacokinetic model for chlordiazepoxide.HCl in the dog.J. Pharm. Sci. 59: 1569–1574 (1970).PubMedCrossRefGoogle Scholar
  18. 18.
    J. G. P. Barnes. Some experiences in the estimation of parameters in non-linear differential equations.FEBS Letters Suppl. 2: S63-S69 (1969).CrossRefGoogle Scholar
  19. 19.
    M. Berman and M. F. Weiss.User's Manual for SAAM, National Institutes of Health, Bethesda, Md., 1968, pp. II-3–II-4.Google Scholar
  20. 20.
    J. G. Wagner, E. Novak, L. G. Leslie, and C. M. Metzler. Absorption, distribution and elimination of spectinomycin dihydrochloride in man.Internat. J. Clin. Pharmacol. 1: 261–285 (1968).Google Scholar
  21. 21.
    R. B. Loftfield and E. A. Eigner. Molecular order of participation of inhibitors (or activators) in biological systems.Science 164: 305–308 (1969).PubMedCrossRefGoogle Scholar
  22. 22.
    M. C. Meyer and D. E. Guttman. The binding of drugs by plasma proteins.J. Pharm. Sci. 57: 895–918 (1968).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1973

Authors and Affiliations

  • Morris Pfeffer
    • 1
  1. 1.Biochemistry DepartmentEndo Laboratories Inc.Garden City

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