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

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.

Author information

1
Bayer HealthCare AG, Bayer HealthCare Pharmaceuticals Global Drug Discovery, Wuppertal, Germany. olaf.weber@bayer.com

Abstract

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.

PMID:
21762205
PMCID:
PMC3269581
DOI:
10.1111/j.1365-2125.2011.04064.x
[Indexed for MEDLINE]
Free PMC Article

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