PK/PD Modeling of β-Blockers in Cardiovascular Disease: An Update

Abstract

For instance, only the S-enantiomer of β-blockers binds to β-adrenoceptor, whereas the R-enantiomer is mainly inactive for first-and second-generation β-blockers agents of the therapeutic group [11]. In the case of third-generation congeners, both R-and S-enantiomer of carvedilol show α 1-adrenergic blocking activity and L-nebivolol induces vasodilatation by an e ndothelial-dependent mechanism [10]. The great diversity of PK and PD properties of the available β-blockers highlights the relevance of the extensive evaluation of PK and PD properties of these agents in order to optimize the outcomes of the treatment of cardiovascular diseases [7]. In this context , differences in the PK/PD of β-blockers seem to influence in the efficacy and safety of these agents in the clinical setting. Effectiveness of β-blockers in the prevention of stroke is lower than other antihyper-tensive agents due to a lesser ability to reduce central blood pressure and to attenuate blood pressure variability [2,12]. A recent meta-analysis has shown that β-blockers seem to be inferior to other classes of blood pressure lowering drugs for the prevention of major cardiovascular disease events, stroke, renal failure and all-cause m ortality in patients with hypertension [13].