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
; 73(2): 219-31, 2012 Feb.
Article
en En
| MEDLINE
| ID: mdl-21762205
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Transferencia de Ésteres de Colesterol
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Hidroxiquinolinas
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Modelos Biológicos
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Alemania