madman
Super Moderator
ABSTRACT
Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated the data regarding pharmacokinetic (PK) parameters, drug-drug interactions, dextrorotatory (D), and levorotatory (L)stereoisomers of nebivolol. The articles related to the PK of nebivolol were retrieved by searchingthe five databases; Google Scholar, PubMed, Cochrane Library, ScienceDirect, and EBSCO. A total of 20 studies comprising plasma concentration-time profile data following the nebivolol’s oral and intravenous (IV) administration were included. The area under the concentration-time curve from zero to infinity (AUC0-1) was 15 times greater in poor metabolizers (PMs) than in extensive metabolizers (EMs). In hypertensive patients, L–nebivolol expressed a higher maximum plasma concentration (Cmax) than D–nebivolol, i.e. 2.5 ng/ml vs 1.2 ng/ml. The AUC0-1 of nebivolol was 3 fold greater in chronic kidney disease (CKD). The clearance (CL) was increased in obese than in controls from 51.6 ± 11.6 L/h to 71.6 ± 17.4 L/h when 0.5 mg/ml IV solution was infused. Nebivolol showed higher Cmax, AUC0-1, and half-life (t1/2) when co-administered with bupropion, duloxetine, fluvoxamine, paroxetine, lansoprazole, and fluoxetine. This concise review of nebivolol would be advantageous in assessing all PK parameters, which may be crucial for clinicians to avoid drug-drug interactions, prevent adverse drug events, and optimize the dosage regimen in diseased patients diagnosed with hypertension and cardiovascular disorders.
1. Introduction
Nebivolol is a third-generation, long-acting, cardioselective b1-adrenoreceptor antagonist, approved by the United States Food and Drug Administration (FDA)in December 2007 for the treatment of hypertension (Wojciechowski and Papademetriou 2008; Fongemieand Felix-Getzik 2015). It is effective in diabetes mellitus, erectile dysfunction, vascular disease, and angina pectoris, along with its off-label use in heart failure (Cheng 2009; Priyadarshni and Curry 2022). Nebivolol is highly selective for the b1 receptor blockade, promoting vasodilation through endothelium-dependent nitric oxide (NO) stimulation (Toblli et al. 2012). Nebivolol differs from other b-blockers due to its unusual vasodilatory activity by L-arginine–NO pathway (Gray and Ndefo 2008). Nebivolol is a racemate of dextrorotatory(D) and levorotatory (L) enantiomers, among which D–nebivolol is involved in b1-receptor blocking activity, whereas L–nebivolol exhibits vasodilator properties (Marketou et al. 2017). It is mainly administered through the extravascular route (Priyadarshni and Curry 2022).
5. Conclusion
This review reveals all the human data of nebivolol regarding its PK parameters, dosage form characteristics, and drug-drug interactions in healthy and diseased participants. The Cmax, Tmax, and AUC0-1 are greater in poor metabolizers than in extensive metabolizers. The CYP2D6 phenotypes do not affect the PK of nebivolol, whereas the AUC0-1 notably increases in CKD patients. This comprehensive review compiles all the PK parameters that could be helpful in the development of PK models. Additionally, it will be convenient for practitioners to predict the dose and eliminate the drug-drug interactions in hypertension, cardiac failure, and renal impairment. Furthermore, it will be beneficial in the amendment of future clinical trials.
Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated the data regarding pharmacokinetic (PK) parameters, drug-drug interactions, dextrorotatory (D), and levorotatory (L)stereoisomers of nebivolol. The articles related to the PK of nebivolol were retrieved by searchingthe five databases; Google Scholar, PubMed, Cochrane Library, ScienceDirect, and EBSCO. A total of 20 studies comprising plasma concentration-time profile data following the nebivolol’s oral and intravenous (IV) administration were included. The area under the concentration-time curve from zero to infinity (AUC0-1) was 15 times greater in poor metabolizers (PMs) than in extensive metabolizers (EMs). In hypertensive patients, L–nebivolol expressed a higher maximum plasma concentration (Cmax) than D–nebivolol, i.e. 2.5 ng/ml vs 1.2 ng/ml. The AUC0-1 of nebivolol was 3 fold greater in chronic kidney disease (CKD). The clearance (CL) was increased in obese than in controls from 51.6 ± 11.6 L/h to 71.6 ± 17.4 L/h when 0.5 mg/ml IV solution was infused. Nebivolol showed higher Cmax, AUC0-1, and half-life (t1/2) when co-administered with bupropion, duloxetine, fluvoxamine, paroxetine, lansoprazole, and fluoxetine. This concise review of nebivolol would be advantageous in assessing all PK parameters, which may be crucial for clinicians to avoid drug-drug interactions, prevent adverse drug events, and optimize the dosage regimen in diseased patients diagnosed with hypertension and cardiovascular disorders.
1. Introduction
Nebivolol is a third-generation, long-acting, cardioselective b1-adrenoreceptor antagonist, approved by the United States Food and Drug Administration (FDA)in December 2007 for the treatment of hypertension (Wojciechowski and Papademetriou 2008; Fongemieand Felix-Getzik 2015). It is effective in diabetes mellitus, erectile dysfunction, vascular disease, and angina pectoris, along with its off-label use in heart failure (Cheng 2009; Priyadarshni and Curry 2022). Nebivolol is highly selective for the b1 receptor blockade, promoting vasodilation through endothelium-dependent nitric oxide (NO) stimulation (Toblli et al. 2012). Nebivolol differs from other b-blockers due to its unusual vasodilatory activity by L-arginine–NO pathway (Gray and Ndefo 2008). Nebivolol is a racemate of dextrorotatory(D) and levorotatory (L) enantiomers, among which D–nebivolol is involved in b1-receptor blocking activity, whereas L–nebivolol exhibits vasodilator properties (Marketou et al. 2017). It is mainly administered through the extravascular route (Priyadarshni and Curry 2022).
5. Conclusion
This review reveals all the human data of nebivolol regarding its PK parameters, dosage form characteristics, and drug-drug interactions in healthy and diseased participants. The Cmax, Tmax, and AUC0-1 are greater in poor metabolizers than in extensive metabolizers. The CYP2D6 phenotypes do not affect the PK of nebivolol, whereas the AUC0-1 notably increases in CKD patients. This comprehensive review compiles all the PK parameters that could be helpful in the development of PK models. Additionally, it will be convenient for practitioners to predict the dose and eliminate the drug-drug interactions in hypertension, cardiac failure, and renal impairment. Furthermore, it will be beneficial in the amendment of future clinical trials.
