Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Interspecies scaling: predicting clearance of anticancer drugs in humans

A comparative study of three different approaches using body weight or body surface area

  • 58 Accesses

  • 8 Citations


From this study it is proposed that the clearance of anti-cancer drugs may be best estimated if they follow the following trend: (i) that if the exponent of the allometric equation (clearance vs body weight) lies between 0.55–0.75 (0.75 was chosen after Kleiber’s power rule (18)), then a simple allometric equation can predict the clearance reasonably well; (ii) if the exponent of the allometric equation lies between 0.75 to approximately 0.90, clearance can be reasonably predicted using CL × MLP; and (iii) if the exponent of the allometric equation is ≥0.90, the clearance can be predicted using the product of clearance and brain weight.

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


  1. 1.

    Heusner A.A. (1987): What does the power function reveal about structure and function in animals of different size. Annu. Rev. Physiol., 78, 121–133.

  2. 2.

    McNamara P.J. (1991): Interspecies scaling in pharmacokinetics. In: Welling P.G., Tse F.L.S., Dighe S.V. (Eds) Pharmaceutical Bioequivalence. New York. Marcel Dekker, pp. 267–300.

  3. 3.

    Boxenbaum H., Murray W., Markin, R., Ciraulo D. (1985): In: Barnett G., Nora C.C. (Eds) Pharmacokinetics and Pharmacodynamics of Psychoactive Drugs. Forest City, CA, USA. Biomedical Publications, p. 93.

  4. 4.

    Voisin E.M., Ruthsatz M., Collins J.M., Hoyle P.C. (1990): Extrapolation of animal toxicity to humans: interspecies comparisons in drug development. Reg. Toxicol. Pharmacol., 12, 107–116.

  5. 5.

    Chappel W.R., Mordenti J. (1991): Extrapolation of toxicological and pharmacological data from animals to humans. Adv. Drug. Res., 20, 1–116.

  6. 6.

    Boxenbaum H. (1984): Interspecies pharmacokinetic scaling and the evolutionary comparative paradigm. Drug Metab. Rev., 15, 1071–1121.

  7. 7.

    Dedrick R.L., Forrester D.D., Cannon J.N., Dareer S.M.E., Mellett B.L. (1973): Pharmacokinetics of 1-β-d-arabinofuranosylcytosine (Ara-C) deamination in several species. Biochem. Pharmacol., 22, 2405–2417.

  8. 8.

    King F.G., Dedrick R.L., Farris F.F. (1986): Physiological pharmacokinetic modeling ofcis-dichlorodiamineplatinum (II) (DDP) in several species. J. Pharmacokinet. Biopharm., 14, 131–155.

  9. 9.

    Paxton J.W., Kim S.N., Whitfield L.R. (1990): Pharmacokinetic and toxicity of the antitumor agents amascrine and CI-921, a new analogue, in mice, rats, rabbits, dogs and humans. Cancer Res., 50, 2692–2697.

  10. 10.

    McGovern P.J., Williams M.G., Stewart J.C. (1988): Interspecies comparison of acivicin pharmacokinetics. Drug. Metab. Dispos., 16, 18–22.

  11. 11.

    Kaye S.B., Workman P., Graham P.A., Cassidy J., Jorell D. (1993): Pharmacokinetics and early clinical studies of selected new drugs. In: Workman P., Graham M.A. (Eds) Pharmacokinetics and Cancer Chemotherapy. Cold Spring Harbor, Cold Spring Harbor Laboratory Press, pp 371–396.

  12. 12.

    Mehta S.C., Lu D.R. (1995): Interspecies pharmacokinetic scaling of BSH in mice, rats, rabbits, and humans: Biopharm. Drug. Dispos., 16, 735–744.

  13. 13.

    Sacher G. (1959): Relation of lifespan to brain weight and body weight in mammals. In: Wolstenholme G.E.W., O’Connor M. (Eds) CIBA Foundation Colloquium on Aging. London, Churchill, pp. 115–133.

  14. 14.

    Dedrick R.L., Bischoff K.B., Zaharko D.Z. (1970): Interspecies correlation of plasma concentration history of methotrexate (NSC-740). Cancer Chemother. Rep., Part 1, 54, 95–101.

  15. 15.

    Mordenti J. (1986): Man versus beast. J. Pharm. Sci., 75, 1028–1040.

  16. 16.

    Boxenbaum H. (1982): Interspecies scaling, allometry, physiological time and the ground plan of pharmacokinetics. J. Pharmacokinet. Biopharm., 10, 201–227.

  17. 17.

    Dedrick R.L. (1973): Animal scale-up. J. Pharmacokinet. Biopharm., 1, 435–461.

  18. 18.

    Kleiber M. (1961): In: The Fire of Life, an Introduction to Animal Energetics. New York, Wiley.

Download references

Author information

Correspondence to I. Mahmood.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mahmood, I. Interspecies scaling: predicting clearance of anticancer drugs in humans. European Journal of Drug Metabolism and Pharmacokinetics 21, 275–278 (1996). https://doi.org/10.1007/BF03189726

Download citation


  • Predicting clearance
  • anticancer drugs
  • man
  • body weight
  • body surface area