Skip to main content
SpringerLink
Log in

Correlation of Unbound Plasma Clearances of Fifteen Extensively Metabolized Drugs Between Humans and Rats

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Unbound plasma clearances (CLu) in humans and rats of 15 extensively metabolized drugs (phe-nytoin, hexobarbital, pentobarbital, phenylbutazone, warfarin, tolbutamide, valproate, phenobarbital, amobarbital, quinidine, chlorpromazine, propranolol, pentazocin, antipyrine, and diazepam), studied earlier by Sawada et al. (J. Pharmacokin. Biopharm. 13:477–491, 1985), were calculated. It was found that the ratio of CLu per square meter of body surface area between human and rat ranged from 0.38 for pentobarbital to 2.34 for tolbutamide, with a mean ratio of 1.07. When body weight (BW) was used for correlation, the mean CLu was proportional to BW 0.657±0.0935. A rationale for the above empirical findings is postulated. The present study seems to indicate the existence of a general similarity or predictability in the CLu of drugs between rats and humans. Low correlations were generally obtained when total (bound and unbound) plasma clearances were used for comparison.

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. Y. Sawada, M. Hanano, Y. Sugiyama, and T. Iga. J. Pharmacokin. Biopharm. 13:477–491 (1985).

    Google Scholar 

  2. H. Boxenbaum. J. Pharmacokin Biopharm. 10:201–227 (1982).

    Google Scholar 

  3. H. Boxenbaum and R. Ronfeld. Am J. Physiol. 245:R768–R744 (1983).

    Google Scholar 

  4. A. Yacobi, J. A. Udall, and G. Levy. Clin. Pharmacol. Ther. 19:552–558 (1976).

    Google Scholar 

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

    Google Scholar 

  6. B. Clark and D. A. Smith. CRC Crit. Rev. Toxicol. 12:343–385 (1983–1984).

    Google Scholar 

  7. J. Mordenti. J. Pharm. Sci. 75:1028–1040 (1986).

    Google Scholar 

  8. G. R. Wilkinson. Pharmacol. Rev. 39:1–47 (1987).

    Google Scholar 

  9. L. B. Mullett. Prog. Drug. Res. 13:136–169 (1969).

    Google Scholar 

  10. U. Klotz, K. H. Antonin, and P. R. Bieck. J. Pharmacol. Exp. Ther. 199:67–73 (1976).

    Google Scholar 

  11. A. J. Glazko. Ther. Drug Monit. 9:180–189 (1987).

    Google Scholar 

  12. E. J. Freireich, E. A. Gehan, D. P. Rall, L. H. Schmidt, and H. E. Skipper. Cancer Chemother. Rep. 50:219–244 (1966).

    Google Scholar 

  13. L. Z. Benet and L. B. Sheiner. In A. G. Gilman, L. S. Goodman, T. W. Rall, and F. Murad (eds.), The Pharmacological Basis of Therapeutics, 7th ed., Macmillan, New York, 1985, pp. 1663–1733.

    Google Scholar 

  14. W. S. Spector. Handbook of Biological Data, W.B. Saunders, Philadelphia, 1956.

    Google Scholar 

  15. F. H. Hsu. Absorption and Disposition of Chlorothiazide in Rats, Ph.D. thesis, University of Illinois at Chicago, 1987.

  16. E. J. Calabrese. Principles of Animal Extrapolation, John Wiley and Sons, New York, 1983.

    Google Scholar 

  17. W. A. Calder, III. Annu. Rev. Physiol. 49:107–120 (1987).

    Google Scholar 

  18. A. A. Heusner. Annu. Rev. Physiol. 49:121–133 (1987).

    Google Scholar 

  19. A. A. Heusner. Resp. Physiol. 48:1–12. (1982).

    Google Scholar 

  20. M. Kleiber. The Fire of Life, an Introduction to Animal Energetics, John Wiley & Sons, New York, 1961.

    Google Scholar 

  21. T. A. McMahon and J. T. Bonner. On Size and Life, Scientific American Books, New York, 1983.

    Google Scholar 

  22. K. Schmidt-Neilsen. Scaling, Why is Animal Size So Important? Cambridge University Press, New York, 1984.

    Google Scholar 

  23. R. L. Dedrick and K. B. Bischoff. Fed. Proc. 39:54–59 (1980).

    Google Scholar 

  24. H. Bartels. Expl. Biol. Med. 7:1–11 (1982).

    Google Scholar 

  25. J. Prothero. J. Theor. Biol. 106:1–8 (1984).

    Google Scholar 

  26. F. H. Hsu, T. Prueksaritanont, M. G. Lee, and W. L. Chiou. Pharm. Res. 3:107S (1986).

    Google Scholar 

  27. F. H. Hsu, T. Prueksaritanont, M. G. Lee, and W. L. Chou. J. Pharmacokin. Biopharm. 15:369–386 (1987).

    Google Scholar 

  28. M. S. Roberts and M. Rowland. J. Pharm. Pharmacol. 38:177–181 (1986).

    Google Scholar 

  29. W. L. Chiou. Int. J. Clin. Pharmacol. Ther. Toxicol. 22:577–590 (1984).

    Google Scholar 

  30. W. L. Chiou. J. Clin. Hosp. Pharm. 7:20–30 (1982).

    Google Scholar 

  31. W. L. Chiou. Res. Commun. Chem. Pathol. Pharmacol. 56:121–124 (1987).

    Google Scholar 

  32. U. Klotz. J. Pharmacokin. Biopharm. 13:347–348 (1985).

    Google Scholar 

  33. M. G. Lee, C. Y. Lui, and W. L. Chiou. Biopharm. Drug. Disp. 7:487–494 (1986).

    Google Scholar 

  34. H. J. Lee, Y. S. Choo, T. M. Chen, and W. L. Chiou. Pharm. Res. 3:152S (1986).

    Google Scholar 

  35. H. Boxenbaum. J. Pharmacokinet. Biopharm. 8:165–176 (1980).

    Google Scholar 

  36. G. Lam and W. L. Chiou. J. Pharm. Pharmacol. 34:132–134 (1982).

    Google Scholar 

  37. G. Lam, M. L. Chen, and W. L. Chiou. J. Pharm. Sci. 71:454–456 (1982).

    Google Scholar 

  38. M. L. Chen, G. Lam, M. G. Lee, and W. L. Chiou. J. Pharm. Sci. 71:1386–1389 (1982).

    Google Scholar 

Download references

Author information

Author notes

  1. Fung-Hwa Hsu

    Present address: Abbott Laboratories, Abbott Park, Illinois, 60064

Authors and Affiliations

  1. Department of Pharmacodynamics (M/C 865), College of Pharmacy, University of Illinois at, Chicago, Illinois, 60612

    Win L. Chiou & Fung-Hwa Hsu

Authors
  1. Win L. Chiou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fung-Hwa Hsu
    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

Chiou, W.L., Hsu, FH. Correlation of Unbound Plasma Clearances of Fifteen Extensively Metabolized Drugs Between Humans and Rats. Pharm Res 5, 668–672 (1988). https://doi.org/10.1023/A:1015935206569

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015935206569

Search

Navigation