New Data for Nebivolol after In Silico PK Study: Focus on Young Patients and Dosage Regimen

Lara Marques; Bárbara Costa; Nuno Vale

doi:10.3390/pharmaceutics14091911

New Data for Nebivolol after In Silico PK Study: Focus on Young Patients and Dosage Regimen

Pharmaceutics. 2022 Sep 9;14(9):1911. doi: 10.3390/pharmaceutics14091911.

Authors

Lara Marques^{1

2}, Bárbara Costa^{1

2}, Nuno Vale^{1

2

3}

Affiliations

¹ OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal.
² CINTESIS@RISE, Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
³ Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal.

Abstract

Nebivolol (NEB) is a highly selective β1 receptor antagonist with a distinct pharmacological profile. This drug is approved for the treatment of hypertension in the US, and hypertension and heart failure in Europe. Here, we review observations based on age dependence and explore new drug regimens with in-silico studies, to achieve better efficacy and safety. The clinical data were obtained from six published literature reports. Then the data were used for model building, evaluation, and simulation. A two-compartment model with first-order absorption, lag time, linear elimination, and the following covariates: age and genotype were the ones best describing our population. Simulation of different dose regimens resulted in an increase chance of efficacy and safety when the dose regimen was altered to 6 mg every 36 h. It is worth noting that our population in this study constituted of young and healthy individuals. Studies regarding the effects of NEB according to age are scarce; however, they are needed to further improve efficacy and safety, and reduce adverse effects.

Keywords: Nebivolol; dosage regimen; in silico pharmacology; population PK.

Grants and funding

This work was financed by FEDER—Fundo Europeu de Desenvolimento Regional through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia, in a framework of the projects in CINTESIS, R&D Unit (reference UIDB/4255/2020) and within the scope of the project “RISE—LA/P/0053/2020”. N.V. also thanks support from FCT and FEDER (European Union), award number IF/00092/2014/CP1255/CT0004 and CHAIR in Onco-Innovation at FMUP.