Encorafenib, a potent BRAF kinase inhibitor undergoes significant metabolism by CYP3A4 (83%) and CYP2C19 (16%) and also a substrate of P-glycoprotein (P-gp).
Mind the Gap: Model-Based Switching from Selatogrel to Maintenance Therapy with Oral P2Y12 Receptor Antagonists
The P2Y12 receptor antagonist selatogrel is being developed for subcutaneous self-administration with a ready-to-use autoinjector at the onset of acute myocardial infarction (AMI)symptoms.
Can an Amine Be a Weaker and a Stronger Base at the Same Time? Curious Cases of Chameleonic Ionization
We discovered an anomalous basic dissociation in certain multiprotic compounds.
Dabigatran Dosing Proposal for Adults With Atrial Fibrillation: Stress-Testing Renal Function Range in Real World Patients
Dabigatran is the first of four direct-acting oral anticoagulants approved to prevent stroke in adult patients with atrial fibrillation using a fixed two-dose scheme compared with warfarin dosing adjusted to...
Physiologically based pharmacokinetic modeling (PBPK) to predict drug-drug interactions for encorafenib. Part II. Prospective predictions in hepatic and renal impaired populations with clinical inhibitors and inducers
Encorafenib, a potent BRAF kinase inhibitor gets significantly metabolised by CYP3A4 (83%) and CYP2C19 (16%) and is a substrate for P-glycoprotein...
Pyronaridine: a review of its clinical pharmacology in the treatment of malaria
Pyronaridine-artesunate was recently strongly recommended in the 2022 update of the WHO Guidelines for the Treatment of Malaria, becoming the...
SubQ-Sim: A Subcutaneous Physiologically Based Biopharmaceutics Model. Part 1: The Injection and System Parameters
To construct a detailed mechanistic and physiologically based biopharmaceutics model capable of predicting 1) device-formulation-tissue interaction during the injection process and 2) binding, degradation, local distribution, diffusion, and drug absorption, following subcutaneous injection.
Selective COX-2 inhibitors after bariatric surgery: Celecoxib, etoricoxib and etodolac post-bariatric solubility/dissolution and pharmacokinetics
Anatomical/physiological gastrointestinal changes after bariatric surgery may influence the fate of orally administered drugs.
A robust, viable, and resource sparing HPLC-based logP method applied to common drugs
Reliable, experimentally determined partition coefficient P (logP) for most drugs are often unavailable in the literature. Many values are from in silico predictions and may not accurately reflect drug lipophilicity.
Halloysite nanotubes-cellulose ether based biocomposite matrix, a potential sustained release system for BCS class I drug verapamil hydrochloride: Compression characterization, in-vitro release kinetics, and in-vivo mechanistic physiologically based pharmacokinetic modeling studies
This study investigated the ability of natural nanotubular clay mineral (Halloysite) and cellulose ether based biocomposite matrix as a controlled release...
Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy
Preterm birth rates and maternal and neonatal mortality remain concerning global health issues, necessitating improved strategies for testing therapeutic compounds during pregnancy.
ADME characterization and PBK model development of 3 highly protein-bound UV filters through topical application
Estimating human exposure in the safety assessment of chemicals is crucial. Physiologically based kinetic (PBK) models which combine information on exposure, physiology, and chemical properties...
AIDD, an interactive AI-driven drug design system that uses molecular evolution and mechanistic pharmacokinetic simulation to optimize multiple property objectives simultaneously
Computer-aided drug design has advanced rapidly in recent years, and multiple instances of in silico designed molecules advancing to the clinic have...
Predicting bioequivalence and developing dissolution bioequivalence safe space in vitro for warfarin using a Physiologically-Based pharmacokinetic absorption model
Bioequivalence (BE) studies support the approval and clinical use of both new and generic drug products.
Training the next generation of pharmacometric modelers: a multisector perspective
The current demand for pharmacometricians outmatches the supply provided by academic institutions and considerable investments are made to develop the competencies of these scientists on-the-job.
Physiologically based pharmacokinetic model combined with reverse dose method to study the nephrotoxic tolerance dose of tacrolimus
Nephrotoxicity is the most common side effect that severely limits the clinical application of tacrolimus (TAC), an immunosuppressive agent used in kidney transplant patients.
The In Vitro, In Vivo, and PBPK Evaluation of a Novel Lung-Targeted Cardiac-Safe Hydroxychloroquine Inhalation Aerogel
Hydroxychloroquine (HCQ) was repurposed for COVID-19 treatment. Subtherapeutic HCQ lung levels and cardiac toxicity of oral HCQ were overcome...
PB2205: A Mechanistic Absorption and Pharmacokinetic Model of Covalent BTK Inhibitor TL-895: Influence of Food and Acid Reducing Agents
L-895 is a highly potent, orally available, selective, covalent inhibitor of Bruton tyrosine kinase (BTK) and bone marrow tyrosine kinase X-linked (BMX)...
Quantitative Systems Toxicology identifies independent mechanisms for hepatotoxicity and bilirubin elevations due to AKR1C3 Inhibitor BAY1128688
BAY1128688 is a selective inhibitor of AKR1C3, investigated recently in a trial that was prematurely terminated due to drug-induced liver injury. These...
Assessing Liver Effects of Cannabidiol and Valproate Alone and in Combination Using Quantitative Systems Toxicology
In clinical trials of cannabidiol (CBD) for the treatment of seizures in patients with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex, elevations in serum alanine...