Clinical pharmacokinetics of nadolol: A systematic review

Abstract

What is known and objective: Nadolol is a non-selective beta-adrenergic antagonist that is used for the treatment of hypertension and angina. The primary route for its administration is oral. It is given once daily as it has a longer half-life (t½). The purpose of conducting this systematic review is to provide a comprehensive view of all the available pharmacokinetic (PK) data on nadolol in humans. This review aimed to systematically collate and analyze publish data on the clinical PK of nadolol in humans and this can be beneficial for the clinicians in dosage adjustments.Methods: Two electronic databases PubMed and Google Scholar were used for conducting a systematic literature search. All the relevant articles containing PK data of nadolol in humans were retrieved. A total of 1275 articles were searched from both databases and after applying eligibility criteria finally, 22 articles were included for conducting the systematic review.Results and discussion: The area under the plasma concentration curve (AUC) and maximum plasma concentration (C max ) of nadolol increased in a dose-dependent manner. The t½ of nadolol was increased to double (18.2-68.6 h) in the patients with chronic kidney disease while the serum t½ became shorter (3.2-4.3 h) when administered to the children. The bioavailability of nadolol was greatly reduced by the coadministration of green tea. Nadolol can be effectively removed by hemodialysis. It undergoes enterohepatic circulation thus activated charcoal decreased its bioavailability.What is new and conclusion: Since, there is no previous report of a systematic review on the PK of nadolol, the current review encompasses all the relevant published articles on nadolol in humans. The analysis and understanding of PK parameters (AUC, C max , and t½) of nadolol may be helpful in the development and evaluation of PK models.

A HPLC-MS/MS method for the determination of Nadolol in rat plasma: Development, validation, and application to pharmacokinetic study

“…Nadolol absorption from the gastrointestinal tract varies and is not influenced by the presence of any concomitant administration. 12 Peak plasma concentration is reached between 3 and 4 h after administration. 13 About 30% bound to plasma proteins with a large volume of distribution (0.3-0.4 L/kg) and it is distributed into extravascular compartments.…”

“…13 About 30% bound to plasma proteins with a large volume of distribution (0.3–0.4 L/kg) and it is distributed into extravascular compartments. 12 The plasma half-life (t½) of Nadolol ranges from 17 to 23 h at therapeutic doses. With a once-daily dosage, the steady-state concentration of Nadolol reaches in 6 to 9 days.…”

Novel Calmodulin Variant p.E46K Associated With Severe Catecholaminergic Polymorphic Ventricular Tachycardia Produces Robust Arrhythmogenicity in Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes

“…Considering the clinical pharmacotherapy in the 2 index patients, we evaluated the antiarrhythmic effects of nadolol and flecainide on the Ca 2+ transients in E46K iPSC-CMs (Figure 7A). Drug concentrations were determined according to the therapeutic plasma concentrations (nadolol: 0.5–1.5 μmol/L, 33 flecainide: 0.5–2.4 μmol/L 34 ). Both nadolol and flecainide suppressed the abnormal Ca 2+ waves in a dose-dependent manner (Figure 7B).…”

“…46 However, we noticed that 4 out of 15 (26.7%) CaM-related patients with CPVT treated with β-blockers experienced severe arrhythmic events, including cardiac arrest and sudden death, indicating insufficient protection (Table S6). 7 Since flecainide, a class Ic antiarrhythmic drug, has been used as an effective therapy in preventing arrhythmias in patients with CPVT who are refractory to β-blockers therapies, 45 we examined the effects of nadolol and flecainide in E46K iPSC-CMs based on clinical settings 33,34 (Figure 7). Both drugs efficiently alleviated abnormal Ca 2+ waves in E46K iPSC-CMs which is consistent with the clinical response in the index patients.…”

A Systematic Critical Review of Clinical Pharmacokinetics of Torasemide

“…It focuses on the presence or absence of randomization, blinding, and descriptions of withdrawals and dropouts. Although it was developed for clinical trials, the authors decided to apply this tool to PK studies because it has been used in previous PK studies 26,27 and many researchers in the field are familiar with it.…”