Prospective allometric scaling: does the emperor have clothes?

J Clin Pharmacol. 2000 Apr;40(4):335-40. doi: 10.1177/00912700022009017.


We are not suggesting that an allometric relationship between pharmacokinetic parameters in animals and humans does not exist; we believe that it does. We are suggesting that using prospective AS to select doses in an FTIM study may lead to a false sense of security given the large publication bias in the literature. There are a number of unrecognized pitfalls to this approach, including (1) prediction intervals so wide as to be of limited use, (2) prediction error is often no better than arbitrarily chosen constants, and (3) it is not possible to determine which drugs will fail a priori. We encourage journals to publish studies in which prospective AS has failed so as scientists we may begin to see what makes these compounds different, with a goal toward better prediction of human pharmacokinetics.

MeSH terms

  • Animals
  • Body Weight
  • Half-Life
  • Humans
  • Longevity
  • Metabolic Clearance Rate
  • Models, Biological
  • Pharmacokinetics*
  • Tissue Distribution