title: Models for evaluating the pharmacokinetics and pharmacodynamics for β-blockers.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Universidad de Buenos Aires, School of Pharmacy and Biochemistry, Facultad de Farmacia y Bioquímica, Department of Pharmacology , Junín 956, (C1113AAD) Buenos Aires , Argentina +54 11 4964 8265 ; +54 11 4508 3645 ; chocht@ffyb.uba.ar.
authors.forename: Christian
authors.initials: C
authors.lastname: Höcht
authors.forename: Facundo Martín
authors.initials: FM
authors.lastname: Bertera
authors.forename: Julieta Sofía
authors.initials: JS
authors.lastname: Del Mauro
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Taira
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological
chemical_list: D000319:Adrenergic beta-Antagonists