Accurate prediction of human clearance (CL) and volume of distribution at steady state (Vd,ss) for small molecule drug candidates is an essential component of assessing likely efficacious dose and clinical safety margins.
Corrosion inhibition and ecotoxicological assessment of 1,2,3-triazolic alcohols
Here, it is reported the synthesis of two triazole derivatives (1-phenyl-1H-1,2,3-triazole-4-yl)methanol (3a) and (1-(4-nitrophenyl)-1H-1,2,3-triazole-4-yl)methanol (3b)) and...
Physiologically Based Pharmacokinetics Modeling in Biopharmaceutics: Case Studies for Establishing the Bioequivalence Safe Space for Innovator and Generic Drugs
For successful oral drug development, defining a bioequivalence (BE) safe space is critical for the identification of newer bioequivalent formulations or for setting of clinically relevant in vitro specifications to ensure drug product quality.
Population pharmacokinetics of vericiguat in patients with heart failure with reduced ejection fraction: an integrated analysis
Vericiguat, a novel stimulator of soluble guanylate cyclase (sGC), is indicated for the treatment of patients following a hospitalization for heart failure or need for outpatient intravenous diuretics, with symptomatic chronic heart failure and ejection fraction less than 45%. Pharmacokinetic (PK) data from the phase II trial SOCRATES-REDUCED (Soluble Guanylate Cyclase Stimulator in Heart Failure Study) and the...
Potent and Broad Neutralization of SARS-CoV-2 Variants of Concern (VOCs) including Omicron Sub-lineages BA.1 and BA.2 by Biparatopic Human VH Domains
The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics with high neutralization breadth.
Preclinical Pharmacokinetic and Pharmacodynamic Investigation of 5’-Methoxynobiletin from Ageratum conyzoides: In vivo and In silico Approaches
5’-methoxynobiletin (5’-MeONB), a polymethoxyflavone isolated from A. conyzoides, has shown anti-inflammatory property. Nevertheless, the antinociceptive...
Identification of a novel immune-inflammatory signature of COVID-19 infections, and evaluation of pharmacokinetics and therapeutic potential of RXn-02, a novel small-molecule derivative of quinolone
Coronavirus disease 2019 (COVID-19) is a global pandemic and respiratory infection that has enormous damage to human lives and economies.
Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton-Pump Inhibitors
Acalabrutinib is a Bruton tyrosine kinase (BTK) inhibitor approved to treat adults with chronic lymphocytic leukemia,small lymphocytic lymphoma, or previously treated mantle cell lymphoma.
Fragment-based drug discovery—the importance of high-quality molecule libraries
Fragment-based drug discovery (FBDD) is now established as a complementary approach to high-throughput screening (HTS).
Understanding Interindividual Variability in the Drug Interaction of a Highly Extracted CYP1A2 Substrate Tizanidine: Application of a Permeability-Limited Multicompartment Liver Model in a Population Based Physiologically Based Pharmacokinetic Framework
Tizanidine, a centrally acting skeletal muscle relaxant, is predominantly metabolized by CYP1A2 and undergoes extensive hepatic first-pass metabolism after oral administration.
Simulation of febuxostat pharmacokinetics in healthy subjects and patients with impaired kidney function using physiologically based pharmacokinetic modeling
Febuxostat is recommended by the American College of Rheumatology Gout Management Guidelines as a first-line therapy for lowering the level of urate in patients with gout.
Impact of Composition and Morphology of Ketoconazole-Loaded Solid Lipid Nanoparticles on Intestinal Permeation and Gastroplus-Based Prediction Studies
Ketoconazole (KTZ) is a potential oral antifungal agent to control systemic and local infections.
From traditional to data-driven medicinal chemistry: A case study
Artificial intelligence (AI) and data science are beginning to impact drug discovery.
Machine Learning guided early drug discovery of small molecules
Machine learning (ML) approaches have been widely adopted within the early stages of the drug discovery process, particularly within the context of small-molecule drug...
Using GastroPlus to teach complex biopharmaceutical concepts
This report showcases the use of the software GastroPlus in an undergraduate-level pharmacy course.
Chronotherapy based on modified-release hydrocortisone to restore the physiological cortisol diurnal rhythm
In this inspirational note, we describe the development of an endocrine chronotherapy to restore the physiological rhythm of the essential adrenal stress hormone, cortisol.
The Use of Physiologically Based Pharmacokinetic Analyses-in Biopharmaceutics Applications -Regulatory and Industry Perspectives
The use of physiologically based pharmacokinetic (PBPK) modeling to support the drug product quality attributes, also known as physiologically based biopharmaceutics modeling...
Physiologically-Based Pharmacokinetics Modeling for Hydroxychloroquine as a Treatment for Malaria and Optimized Dosing Regimens for Different Populations
Malaria is a severe parasite infectious disease with high fatality.
Comparing the Liver Safety Profiles of 4 Next-Generation CGRP Receptor Antagonists to the Hepatotoxic CGRP Inhibitor Telcagepant Using Quantitative Systems Toxicology Modeling
Calcitonin gene-related peptide (CGRP) signaling inhibitors have shown efficacy in both the acute and preventive treatment of migraine.
Molluskicidal activity of 3-aryl-2-hydroxy-1,4-naphthoquinones against Biomphalaria glabrata
Schistosomiasis is the second most prevalent parasitic infectious disease after malaria, which affects millions of people worldwide and causes health and socioeconomic...