Skip to main content

Approaches for predicting human pharmacokinetics using interspecies pharmacokinetic scaling

Archives of Pharmacal Research volume 34, pages 1779–1788 (2011)Cite this article

Abstract

Reliably predicting pharmacokinetic behavior in humans from preclinical data is an important aspect of drug development. The most widely used technique in this regard is allometric scaling. In this review, various approaches developed for predicting pharmacokinetic parameters in humans using interspecies scaling are introduced and discussed. Methods to predict plasma concentration-time profiles in humans after intravenous and oral administration are also reviewed. The reliable prediction of human pharmacokinetics with regard to investigational drugs is aimed, ultimately, at selecting the first in-human dose with which to begin clinical studies. Approaches for the selection of the first in-human dose are also reviewed. Although there have been many trials to compare and optimize interspecies scaling methods, no firm conclusions have been reached. Because interspecies scaling methods are still highly empirical, further effort is needed to improve the reliability of predicting human pharmacokinetics by interspecies scaling.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  • Adolph, E. F., Quantitative relations in the physiological constitutions of mammals. Science, 109, 579–585 (1949).

    PubMed  Article  CAS  Google Scholar 

  • Bae, S. K., Lee, S. J., Kim, Y. G., Kim, S. H., Kim, J. W., Kim, T., and Lee, M. G., Interspecies pharmacokinetic scaling of oltipraz in mice, rats, rabbits and dogs, and prediction of human pharmacokinetics. Biopharm. Drug Dispos., 26, 99–115 (2005).

    PubMed  Article  CAS  Google Scholar 

  • Blackwell, B. and Martz, B. L., For the first time in man. Clin. Pharmacol. Ther., 13, 812–826 (1972).

    PubMed  CAS  Google Scholar 

  • Boxenbaum, H., Interspecies variation in liver weight, hepatic blood flow, and antipyrine intrinsic clearance: extrapolation of data to benzodiazepines and phenytoin. J. Pharmacokinet. Biopharm., 8, 165–176 (1980).

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Boxenbaum, H. and Ronfeld, R., Interspecies pharmacokinetic scaling and the Dedrick plots. Am. J. Physiol., 245, R768–R775 (1983).

    PubMed  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Boxenbaum, H. and Fertig, J. B., Scaling of antipyrine intrinsic clearance of unbound drug in 15 mammalian species. Eur. J. Drug Metab. Pharmacokinet., 9, 177–183 (1984).

    PubMed  Article  CAS  Google Scholar 

  • Boxenbaum, H. and DiLea, C., First-time-in-human dose selection: allometric thoughts and perspectives. J. Clin. Pharmacol., 35, 957–966 (1995).

    PubMed  CAS  Google Scholar 

  • Chiou, W. L. and Barve, A., Linear correlation of the fraction of oral dose absorbed of 64 drugs between humans and rats. Pharm. Res., 15, 1792–1795 (1998).

    PubMed  Article  CAS  Google Scholar 

  • Chiou, W. L., Robbie, G., Chung, S. M., Wu, T. C., and Ma, C., Correlation of plasma clearance of 54 extensively metabolized drugs between humans and rats: mean allometric coefficient of 0.66. Pharm. Res., 15, 1474–1479 (1998).

    PubMed  Article  CAS  Google Scholar 

  • Dedrick, R., Bischoff, K. B., and Zaharko, D. S., Interspecies correlation of plasma concentration history of methotrexate (NSC-740). Cancer Chemother. Rep., 54, 95–101 (1970).

    PubMed  CAS  Google Scholar 

  • Feng, M. R., Lou, X., Brown, R. R., and Hutchaleelaha, A., Allometric pharmacokinetic scaling: towards the prediction of human oral pharmacokinetics. Pharm. Res., 17, 410–418 (2000).

    PubMed  Article  CAS  Google Scholar 

  • Iavarone, L., Hoke, J. F., Bottacini, M., Barnaby, R., and Preston, G. C., First time in human for GV196771: interspecies scaling applied on dose selection. J. Clin. Pharmacol., 39, 560–566 (1999).

    PubMed  Article  CAS  Google Scholar 

  • Izumi, T., Enomoto, S., Hosiyama, K., Sasahara, K., Shibukawa, A., Nakagawa, T., and Sugiyama, Y., Prediction of the human pharmacokinetics of troglitazone, a new and extensively metabolized antidiabetic agent, after oral administration, with an animal scale-up approach. J. Pharmacol. Exp. Ther., 277, 1630–1641 (1996).

    PubMed  CAS  Google Scholar 

  • Jolivette, L. J. and Ward, K. W., Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure. J. Pharm. Sci., 94, 1467–1483 (2005).

    PubMed  Article  CAS  Google Scholar 

  • Kang, H. E., Jung, H. Y., Cho, Y. K., Kim, S. H., Sohn, S. I., Baek, S. R., and Lee, M. G., Pharmacokinetics of liquiritigenin in mice, rats, rabbits, and dogs, and animal scaleup. J. Pharm. Sci., 98, 4327–4342 (2009).

    PubMed  Article  CAS  Google Scholar 

  • Ling, J., Zhou, H., Jiao, Q., and Davis, H. M., Interspecies scaling of therapeutic monoclonal antibodies: initial look. J. Clin. Pharmacol., 49, 1382–1402 (2009).

    PubMed  Article  CAS  Google Scholar 

  • Mahmood, I. and Balian, J. D., Interspecies scaling: predicting pharmacokinetic parameters of antiepileptic drugs in humans from animals with special emphasis on clearance. J. Pharm. Sci., 85, 411–414 (1996a).

    PubMed  Article  CAS  Google Scholar 

  • Mahmood, I. and Balian, J. D., Interspecies scaling: predicting clearance of drugs in humans. Three different approaches. Xenobiotica, 26, 887–895 (1996b).

    PubMed  Article  CAS  Google Scholar 

  • Mahmood, I. and Yuan, R., A comparative study of allometric scaling with plasma concentrations predicted by speciesinvariant time methods. Biopharm. Drug Dispos., 20, 137–144 (1999).

    PubMed  Article  CAS  Google Scholar 

  • Mahmood, I., Interspecies scaling: predicting oral clearance in humans. Am. J. Ther., 9, 35–42 (2002).

    PubMed  Article  Google Scholar 

  • Mahmood, I. and Sahajwalla, C., Interspecies scaling of biliary excreted drugs. J. Pharm. Sci., 91, 1908–1914 (2002).

    PubMed  Article  CAS  Google Scholar 

  • Mahmood, I., Green, M. D., and Fisher, J. E., Selection of the first-time dose in humans: comparison of different approaches based on interspecies scaling of clearance. J. Clin. Pharmacol., 43, 692–697 (2003).

    PubMed  CAS  Google Scholar 

  • Miners, J. O., Knights, K. M., Houston, J. B., and Mackenzie, P. I., In vitro-in vivo correlation for drugs and other compounds eliminated by glucuronidation in humans: pitfalls and promises. Biochem. Pharmacol., 71, 1531–1539 (2006).

    PubMed  Article  CAS  Google Scholar 

  • Mordenti, J., Man versus beast: pharmacokinetic scaling in mammals. J. Pharm. Sci., 75, 1028–1040 (1986).

    PubMed  Article  CAS  Google Scholar 

  • Mukai, H., Watanabe, S., Tsuchida, K., and Morino, A., Pharmacokinetics of NS-49, a phenethylamine class alpha (1A)-adrenoceptor agonist, at therapeutic doses in several animal species and interspecies scaling of its pharmacokinetic parameters. Int. J. Pharm., 186, 215–222 (1999).

    PubMed  Article  CAS  Google Scholar 

  • Nagilla, R. and Ward, K. W., A comprehensive analysis of the role of correction factors in the allometric predictivity of clearance from rat, dog, and monkey to humans. J. Pharm. Sci., 93, 2522–2534 (2004).

    PubMed  Article  CAS  Google Scholar 

  • Obach, R. S., Baxter, J. G., Liston, T. E., Silber, B. M., Jones, B. C., MacIntyre, F., Rance, D. J., and Wastall, P., The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J. Pharmacol. Exp. Ther., 283, 46–58 (1997).

    PubMed  CAS  Google Scholar 

  • Puigdemont, A., Ramis, J., Guitart, R., and Arboix, M., Species scaling of propafenone disposition and concentrationtime relationships among eight mammalian species. J. Pharm. Sci., 82, 1126–1129 (1993).

    PubMed  Article  CAS  Google Scholar 

  • Reigner, B. G. and Blesch, K. S., Estimating the starting dose for entry into humans: principles and practice. Eur. J. Clin. Pharmacol., 57, 835–845 (2002).

    PubMed  Article  CAS  Google Scholar 

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

    Google Scholar 

  • Sinha, V. K., De Buck, S. S., Fenu, L. A., Smit, J. W., Nijsen, M., Gilissen, R. A., Van Peer, A., Lavrijsen, K., and Mackie, C. E., Predicting oral clearance in humans: how close can we get with allometry? Clin. Pharmacokinet., 47, 35–45 (2008).

    PubMed  Article  CAS  Google Scholar 

  • Tang, H. and Mayersohn, M., A mathematical description of the functionality of correction factors used in allometry for predicting human drug clearance. Drug Metab. Dispos., 33, 1294–1296 (2005a).

    PubMed  Article  CAS  Google Scholar 

  • Tang, H. and Mayersohn, M., A novel model for prediction of human drug clearance by allometric scaling. Drug Metab. Dispos., 33, 1297–1303 (2005b).

    PubMed  Article  CAS  Google Scholar 

  • Tang, H. and Mayersohn, M., Response to comments on “A mathematical description of the functionality of correction factors used in allometry for predicting human drug clearance.” Drug Metab. Dispos., 34, 510–511 (2006).

    CAS  Google Scholar 

  • Tang, H., Hussain, A., Leal, M., Mayersohn, M., and Fluhler, E., Interspecies prediction of human drug clearance based on scaling data from one or two animal species. Drug Metab. Dispos., 35, 1886–1893 (2007).

    PubMed  Article  CAS  Google Scholar 

  • Tyl, R. W., Developmental toxicology. In Ballatyne, B., Marrs, T., and Turner, P. (Eds.), General and applied toxicology, vol. 1. Stockton Press, New York, p. 1032, (1993).

    Google Scholar 

  • U.S. Food and Drug Administration, Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers (2005).

  • Vaidya, A. B. and Vaidya, R. A., Initial human trials with an investigational new drug (phase I and 2): planning an management. J. Postgrad. Med., 27, 197–213 (1981).

    PubMed  CAS  Google Scholar 

  • Wajima, T., Fukumura, K., Yano, Y., and Oguma, T., Prediction of human clearance from animal data and molecular structural parameters using multivariate regression analysis. J. Pharm. Sci., 91, 2489–2499 (2002).

    PubMed  Article  CAS  Google Scholar 

  • Wajima, T., Fukumura, K., Yano, Y., and Oguma, T., Prediction of human pharmacokinetics from animal data and molecular structural parameters using multivariate regression analysis: volume of distribution at steady state. J. Pharm. Pharmacol., 55, 939–949 (2003a).

    PubMed  Article  CAS  Google Scholar 

  • Wajima, T., Fukumura, K., Yano, Y., and Oguma, T., Predic tion of human pharmacokinetics from animal data and molecular structural parameters using multivariate regression analysis: oral clearance. J. Pharm. Sci., 92, 2427–2440 (2003b).

    PubMed  Article  CAS  Google Scholar 

  • Wajima, T., Yano, Y., Fukumura, K., and Oguma, T., Prediction of human pharmacokinetic profile in animal scale up based on normalizing time course profiles. J. Pharm. Sci., 93, 1890–1900 (2004).

    PubMed  Article  CAS  Google Scholar 

  • Ward, K. W., Azzarano, L. M., Bondinell, W. E., Cousins, R. D., Huffman, W. F., Jakas, D. R., Keenan, R. M., Ku, T. W., Lundberg, D., Miller, W. H., Mumaw, J. A., Newlander, K. A., Pirhalla, J. L., Roethke, T. J., Salyers, K. L., Souder, P. R., Stelman, G. J., and Smith, B. R., Preclinical pharmacokinetics and interspecies scaling of a novel vitronectin receptor antagonist. Drug Metab. Dispos., 27, 1232–1241 (1999).

    PubMed  CAS  Google Scholar 

  • Ward, K. W. and Smith, B. R., A comprehensive quantitative and qualitative evaluation of extrapolation of intravenous pharmacokinetic parameters from rat, dog, and monkey to humans. I. Clearance. Drug Metab. Dispos., 32, 603–611 (2004).

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. College of Pharmacy, The Catholic University of Korea, Bucheon, 420-743, Korea

    Hee Eun Kang & Myung Gull Lee

Authors
  1. Hee Eun Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myung Gull Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hee Eun Kang or Myung Gull Lee.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kang, H.E., Lee, M.G. Approaches for predicting human pharmacokinetics using interspecies pharmacokinetic scaling. Arch. Pharm. Res. 34, 1779–1788 (2011). https://doi.org/10.1007/s12272-011-1101-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-011-1101-4

Key words

  • Allometric scaling
  • Interspecies scaling
  • Preclinical pharmacokinetics
  • Human pharmacokinetic predictions