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Limited Sampling Strategy for Predicting the Area under Plasma Concentration-Time Curve of Nadolol in Healthy Subjects.
J Clin Pharmacol
November 2024
Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University School of Medicine, Fukushima, Japan.
Nadolol is a hydrophilic β-adrenoceptor blocker with a relatively long half-life and negligible metabolism. It is a substrate of P-glycoprotein and organic anion transporting polypeptide 1A2, and may serve as an in vivo probe drug for the assessment of drug-drug and food-drug interactions mediated by these transporters. In the present study, we aimed to develop limited sampling strategy (LSS) models for predicting the area under the plasma concentration-time curve (AUC) of nadolol.
View Article and Find Full Text PDFEffects of Age and Exposure Duration on the Sensitivity of Early Life Stage Fathead Minnow (Pimephales promelas) to Waterborne Propranolol Exposure.
Environ Toxicol Chem
April 2024
Center for Computational Toxicology and Chemistry, US Environmental Protection Agency, Cincinnati, Ohio.
Article Synopsis
- Propranolol, a commonly prescribed medication, is often found in wastewater, raising concerns about its impact on aquatic life, particularly in fathead minnows exposed at various developmental stages.
- The study measured the fish's transcriptional responses to different concentrations of propranolol over specific timeframes, revealing that older fish (over 7 days post-fertilization) were more sensitive to its effects.
- Findings suggest that traditional toxicity testing may underestimate risks since it typically involves younger fish that haven't reached significant developmental milestones, potentially affecting how chemicals like propranolol are understood in terms of environmental impact.
The Promises of Proteomics and Metabolomics for Unravelling the Mechanism and Side Effect Landscape of Beta-Adrenoceptor Antagonists in Cardiovascular Therapeutics.
OMICS
March 2023
Department of Biotechnology, Indian Institute of Technology Hyderabad, Sangareddy, India.
Article Synopsis
- * While beta-blockers are crucial for managing conditions like hypertension and chronic heart failure, they come with side effects and individual variations in how they're processed by the body.
- * New technologies in mass spectrometry and metabolomics are helping researchers better understand the side effects and mechanisms of beta-blockers, including the importance of dosing times to maximize effectiveness and minimize toxicity.
Metabolic Activation and Cytotoxicity of Propafenone Mediated by CYP2D6.
Chem Res Toxicol
May 2022
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P. R. China.
Propafenone (PPF) is a class I antidysrhythmic drug, which is commonly used for the treatment of atrial fibrillation and other supraventricular arrhythmias. It is also a β-adrenoceptor antagonist that can cause bradycardia and bronchospasm. Hepatotoxicity is one of the adverse reactions reported, with clinical manifestations including acute cholestasis and hepatocyte necrosis.
View Article and Find Full Text PDFUrinary Excretion of Nadolol as a Possible In Vivo Probe for Drug Interactions Involving P-Glycoprotein.
J Clin Pharmacol
June 2021
Department of Pharmacy, Fukushima Medical University Hospital, Fukushima, Japan.
Nadolol is a hydrophilic and nonselective β-adrenoceptor blocker with a bioavailability of 30%, relatively longer half-life, negligible metabolism, and predominant renal excretion. Previous studies have reported that nadolol is a substrate of P-glycoprotein, and the coadministration with itraconazole, a typical P-glycoprotein inhibitor, results in elevated plasma concentrations and cumulative urinary excretion of nadolol. In this study, we assessed whether measurements of urinary-excreted nadolol can be an alternative method of plasma pharmacokinetics for P-glycoprotein-mediated drug interactions in humans.
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