A Pharmacokinetic/Pharmacodynamic Model for Cardiovascular Safety Assessment of R1551

Pharmacokinetic-pharmacodynamic relationships are crucial in understanding a drug’s arrhythmogenic potential. Models assist to quantitatively relate parent and metabolite concentrations to adverse electrocardiographic effects, including an apparent delay between effect and circulating parent species concentration. Here, we used an effect compartment model to investigate PR and QRS prolongation previously observed in preclinical studies with the NK1-NK3 antagonist R1551.


Author(s): Angèle Fleury, Thierry Lavé, Fredrik Jonsson, Monique Schmitt, Gerard Hirkaler, Liudmila Polonchuk, Alexander Breidenbach

Year: 2010 年 8 月 21 日

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