Kidney Injury Molecule 1 (KIM-1) is a specific and sensitive biomarker for drug-induced kidney injury (AKI) prediction...
Clinical Ocular Exposure Extrapolation Using PBPK Modeling and Simulation: Levofloxacin Solution Case Study
Development of generic ophthalmic drug products is challenging due to the complexity of the ocular system and a lack of sensitive testing tools to evaluate its interplay with ophthalmic formulations
Assessing the Potential for Hepatotoxicity for Combination Therapy of Valproate (VPA) and Cannabidiol (CBD) using Quantitative Systems Toxicology (QST)
Highly purified cannabidiol (CBD) (approved as Epidiolex in the US) is efficacious in treating seizures associated with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and Tuberous Sclerosis Complex (TSC).
Quantitative Systems Pharmacology Modeling Using NAFLDsym Recapitulated Clinically Observed Histological Responses and Serum Markers to NGM282 in NASH Patients
Nonalcoholic steatohepatitis (NASH) is a growing clinical concern, but currently there is no approved medicine for treatment of NASH. Fibroblast growth...
Gender Related Differences and Pregnancy Induced Changes in Labetalol Glucuronidation Assessed via PBPK Modeling and Simulation
Glucuronidation is considered a major metabolic pathway for drugs containing carboxylic acid, hydroxyl, and amine moieties [1].
Predicting the Efficacy of Obeticholic Acid Treatment for Non-Alcoholic Steatohepatitis (NASH) Using NAFLDsym, a Quantitative Systems Pharmacology Model of Non-Alcoholic Fatty Liver Disease
Obeticholic acid (OCA), a bile acid analog and agonist of the farnesoid X receptor (FXR), is currently in clinical trials...
Relationship Between Pimavanserin Exposure and QTc Interval in Patients with Schizophrenia: Modelling Analysis from Randomized, Double-Blind, Placebo-Controlled Studies
Patients with schizophrenia who are receiving more than one antipsychotic may be at higher risk for QT interval...
Pharmacokinetic Profile of Pimavanserin in Patients With Dementia-Related Psychosis and Concomitant Acetylcholinesterase Inhibitor Use: Modeling Data From the Phase 3 HARMONY Study
Pimavanserin is a selective serotonin-modulating agent with inverse agonist/antagonist activity at the 5HT2A receptor, and to a lesser extent at...
Model-based dose selection for the phase 3 evaluation of molnupiravir (MOV) in the treatment of COVID-19 in adults
There is an urgent need for effective treatment options that are easily administered and readily implementable in health systems globally to reduce the impact of COVID-191
Relationship Between Pimavanserin Exposure and Negative Symptoms in Patients With Schizophrenia: Data Analysis From the Phase 2 ADVANCE Study
Negative symptoms in schizophrenia are associated with poor psychosocial function and long-term outcomes yet no pharmacological treatments are currently approved in the United States to treat...
Using Quantitative Systems Pharmacology Modeling to Understand the Pathophysiology of Idiopathic Pulmonary Fibrosis
Patients with idiopathic pulmonary fibrosis (IPF) have a poor survival prognosis and limited treatment options.
Quantitative Systems Toxicology Modeling Using DILIsym Suggests That Drug-Induced Liver Injury (DILI) Can Be Enhanced by Co-administered Drugs and Mitigated by Mitochondrial Biogenesis
Drug-induced liver injury (DILI) can be enhanced by polypharmacy if co-administered drugs induce toxicity via mechanisms that have overlapping pathways.
A Phase 1b Study of Oral Chk1 Inhibitor LY2880070 as Monotherapy in Patients with Advanced or Metastatic Cancer
In the context of DNA damage, Checkpoint Kinase 1 (Chk1) mediates a checkpoint response which arrests the cell cycle and allows the cell to complete DNA repair and replication.
Relationship between pimavanserin exposure and psychosis relapse in patients with dementia-related psychosis: clinical results and modeling analysis from the phase 3 HARMONY study
Dementia-related psychosis impacts more than 2.4 million patients;1-5 however, there are no
Population pharmacokinetics of MYL-1401O (a trastuzumab biosimilar) and reference trastuzumab (Herceptin®) in patients with HER2-positive metastatic breast cancer
Mylan trastuzumab (MYL-1401O) is a biosimilar to trastuzumab (Herceptin®)
Quantitative systems toxicology (DILIsym) modeling of the acetaminophen (paracetamol) mode of action (MOA) pathway for hepatotoxicity supports that acetaminophen is not a carcinogenic hazard in humans
Acetaminophen has a long history of safe use at therapeutic doses, but can cause liver injury at very high doses
Assessment of the Mechanism for Remdesivir-Associated Clinical ALT Elevations Using DILIsym Quantitative Systems Toxicology Modeling
Remdesivir, a monophosphoramidate prodrug of a nucleoside analog, has been granted Emergency Use Authorization in the U.S. for the treatment of hospitalized COVID-19 patients.
Mathematical Modeling with NAFLDsym Supports the Role of Adiponectin in the Reduction of Steatosis by the Anti-FGFR1/KLB Bispecific Antibody
The agonist anti-FGFR1/KLB bispecific antibody, BFKB8488A, has been shown to be effective at reducing liver fat in NAFLD patients in a Ph1b study [1].
Development of Quantitative Systems Toxicology Model to Predict Drug Induced Acute Kidney Injury via mtDNA Depletion Pathway
Treatment of chronic viral infections like HIV, Hepatitis B etc necessitates long term administration of powerful antivirals like...
Mechanistic Modeling of Cyclosporine A-induced Acute Kidney Injury with RENAsym®
The use of Cyclosporine A (CsA) can cause tubular damage leading to a decline in renal function as determined by decreases in serum creatinine levels...