Skip to main content
Log in

Metabolite Formation Pharmacokinetics: Rate and Extent of Metabolite Formation Determined by Deconvolution

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

A two-step analytic procedure to determine the rate and extent of metabolite production following administration of the parent compound is described. The procedure provides the rate and extent of metabolite production as a function of time by application of the general model independent approach of deconvolution. The metabolite unit impulse response function is obtained by implicit deconvolution of the metabolite data with a truncated constant-rate metabolite input function. Then the obtained unit impulse response function is used in an analytic deconvolution with metabolite data following administration of the parent compound to obtain the rate and extent of metabolite production. The input function is also deconvolved with metabolite data to obtain the unit impulse response function appropriate for prediction of metabolite levels given a selected input of parent compound. The expected profile following administration of the consecutive infusions of parent drug is shown for both parent and metabolite. The rationale for selection of deconvolution methods is discussed. The approach is applied to data for procainamide and N-acetylprocainamide from three human subjects. The results indicate that from 27 to 39% of the procainamide was converted to N-acetylprocainamide in these subjects.

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

Access this article

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. M. Gibaldi and D. Perrier. Pharmacokinetics, 2nd ed., Marcel Dekker, New York, 1982.

    Google Scholar 

  2. T. Sutfin and W. Jusko. In G. Wilkinson and M. Rawlins (eds.), Drug Metabolism and Disposition in Clinical Pharmacology, MTP Press, Boston, 1985, pp. 91–159

    Google Scholar 

  3. S. K. Pang and K. C. Kwan. Drug Metab. Disp. 11:79–84 (1983).

    Google Scholar 

  4. P. Veng-Pedersen. J. Pharm. Sci. 70:32–38 (1981).

    Google Scholar 

  5. M. D. Karol, P. Veng-Pedersen, and R. E. Brashear. J. Pharmacokinet. Biopharm. 11:373–387 (1983).

    Google Scholar 

  6. D. Cutler. J. Pharmacokinet. Biopharm. 6:227–241 (1978).

    Google Scholar 

  7. W. Gillespie and P. Veng-Pedersen. Biopharm. Drug Dispos. 6:351–355 (1985).

    Google Scholar 

  8. P. Veng-Pedersen. J. Pharmacokinet. Biopharm. 8:463–481 (1980).

    Google Scholar 

  9. S. K. Pang. J. Pharmacokinet. Biopharm. 13:633–663 (1985).

    Google Scholar 

  10. J. Wagner, J. Pharmacokinet. Biopharm. 3:457–471 (1975).

    Google Scholar 

  11. D. Vaughan and M. Dennis. J. Pharm. Sci. 67:663–665 (1978).

    Google Scholar 

  12. J. S. Dutcher, J. M. Strong, S. V. Lucas, W. Lee, and A. Atkinson, Jr. Clin. Pharmacol. Ther. 22:447–457 (1977).

    Google Scholar 

  13. P. Veng-Pedersen. J. Pharmacokinet. Biopharm. 5:513–531 (1977).

    Google Scholar 

  14. R. F. Minchin, K. F. Ilett, and J. W. Patterson. Eur. J. Pharmacol. 47:51–56 (1978).

    Google Scholar 

  15. E. E. Bagwell, T. Walle, D. E. Drayer, et al. J. Pharmacol. Exp. Ther. 197:38–48 (1976).

    Google Scholar 

  16. R. D. Reynolds, W. E. Burmeister, S. V. Calzadilla, et al. Proc. Soc. Exp. Biol. Med. 169:156–160 (1982).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karol, M.D., Goodrich, S. Metabolite Formation Pharmacokinetics: Rate and Extent of Metabolite Formation Determined by Deconvolution. Pharm Res 5, 347–351 (1988). https://doi.org/10.1023/A:1015951426191

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015951426191

Navigation