Prediction of a potentially effective dose in humans for BAY 60-5521, a potent inhibitor of cholesteryl ester transfer protein (CETP) by allometric species scaling and combined pharmacodynamic and physiologically-based pharmacokinetic modelling

Br J Clin Pharmacol. 2012 Feb;73(2):219-31. doi: 10.1111/j.1365-2125.2011.04064.x.


Aims: The purpose of this work was to support the prediction of a potentially effective dose for the CETP-inhibitor, BAY 60-5521, in humans.

Methods: A combination of allometric scaling of the pharmacokinetics of the CETP-inhibitor BAY 60-5521 with pharmacodynamic studies in CETP-transgenic mice and in human plasma with physiologically-based pharmacokinetic (PBPK) modelling was used to support the selection of the first-in-man dose.

Results: The PBPK approach predicts a greater extent of distribution for BAY 60-5521 in humans compared with the allometric scaling method as reflected by a larger predicted volume of distribution and longer elimination half-life. The combined approach led to an estimate of a potentially effective dose for BAY 60-5521 of 51 mg in humans.

Conclusion: The approach described in this paper supported the prediction of a potentially effective dose for the CETP-inhibitor BAY 60-5521 in humans. Confirmation of the dose estimate was obtained in a first-in-man study.

MeSH terms

  • Animals
  • Biometry
  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hydroxyquinolines / administration & dosage*
  • Hydroxyquinolines / pharmacokinetics
  • Hydroxyquinolines / pharmacology
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Biological*
  • Rats
  • Rats, Wistar


  • BAY 60-5521
  • Cholesterol Ester Transfer Proteins
  • Hydroxyquinolines