Models for evaluating the pharmacokinetics and pharmacodynamics for β-blockers

Abstract

Introduction: β-blocker therapy plays an important role in the treatment of various diseases, including hypertension, myocardial infarction and heart failure. Although all β-blockers shared their ability to competitively block β₁-adrenoceptor, this therapeutic class showed great heterogeneity in their pharmacokinetic (PK) and pharmacodynamic (PD) properties.

Areas covered: The present review describes the models used for PK and PK/PD evaluation of β-blockers and their applicability in preclinical and clinical studies. PK behavior of different β-blockers has been studied by means of individual compartmental and population PKs, allowing the estimation of relevant PK parameters and factors involved in intersubject variability. Different PK/PD models have been developed for the in vivo estimation of PD parameters of different cardiovascular effects of β-blockers.

Expert opinion: PK models and PK/PD modeling have clearly contributed to characterization of the PK and PD properties of β-blockers. Differences in cardiovascular actions between classical β-blockers and vasodilatory β-blockers need to be further studied in order to confirm the clinical benefits of the new-generation of β-blockers. PK/PD modeling may contribute to clarify the importance of heterogeneity of PK and PD properties of β-blockers potentially improving the selection of the adequate agent and dose regimen in the treatment of cardiovascular diseases.

Keywords::

• blood pressure
• heart rate
• pharmacokinetic–pharmacodynamic modeling
• population pharmacokinetics
• β blockers

Acknowledgements

CA Taira is Career Investigators from CONICET, Argentina.

Declaration of interest

Funding for this paper has been received from the University of Buenos Aires. The authors do not have any potential conflict of interest to declare.

Notes

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