MembranePlus™ – a software platform for simulaton of drug transport in cell assays.
Lead Antimalarial Identification Using in silico Prediction Methods and Simulation
With increasing resistance to currently available antimalarials, new compounds with activity against resistant parasites are needed. Novel compounds were designed and first-in-human (FIH) simulations...
QSP Modeling of Liver AMPK Activation Using NAFLDsym Is Predicted to Reduce Steatosis in NAFLD Patients
Non-alcoholic fatty liver disease (NAFLD) currently has few available treatment options. Bringing effective treatments rapidly to market is paramount.
Mechanistic Modeling And Hepatic Biomarker Data From Ggf2 (Cimaglermin Alfa)-Treated Subjects In Phase 1 Clincial Trials Suggest Low Likelihood Of Progressive Liver Injury
GGF2 (USAN cimaglermin alfa) is an investigational drug for the treatment of heart failure. During Phase 1 clinical trials, concomitant, transient elevations in serum aminotransferases (ALT/AST) and...
Use Of Systems Toxicology Modeling To Investigate Mechanisms Of Liver Enzyme Elevations Mediated By Solithromycin And Other Macrolides
Solithromycin, a 4th generation macrolide developed for the treatment of community acquired pneumonia, caused serum liver enzyme (ALT) elevations in clinical studies.
Using Systems Pharmacology Modeling to Understand the Pathophysiology of NAFLD and Response to Dietary Intervention in a Simulated Population
Non-alcoholic fatty liver disease (NAFLD) can be effectively treated by weight loss, but identifying the underlying responsible mechanisms has been difficult because of the multifactorial pathophysiology.
Quantitative Systems Toxicology Analysis of In Vitro Mechanistic Assays Reveals Importance of Bile Acid Accumulation in TAK-875-induced Liver Injury
TAK-875 (fasiglifam), a GPR40 agonist in development for treatment of type 2 diabetes, was voluntarily terminated in phase 3 due to adverse liver effects.
Development of Physiologically Based Pharmacokinetic (PBPK) Model for Simulating the Disposition of Antibody Drug Conjugates
Antibody- drug conjugates (ADCs) are a novel class of therapeutic agents that deliver potentcy totoxic drug molecules (payload) to their targets while reducing systemic exposure. ADCs may be composed of...
Simulation of in vitro Caco-2 Papp from Molecular Structure Estimation of Intracellular Km for Efflux Transporters
To build in silico models based on molecular structure that estimate the rate of passive diffusion into and out of the cell membrane and to combine those estimates with a cellular simulation of Caco-2...
Modeling of Cilostazol absorption and pharmacokinetics in Beagle Dogs and design of in-vitro dissolution experiment to model the in-vivo absorption
The purpose of this study was to evaluate the in-vitro/in-vivo (IVIV) correlationfor a Class II compound and to design an in-vitro dissolution experiment that improves this IVIV correlation by taking...
Modeling and Simulation Strategy to Support Eslicarbazepine Acetate (ESL) Development in Pediatric Patients in the Treatment of Partial-Onset Seizures
Eslicarbazepine acetate (ESL, Aptiom®) was FDA approved for adjunctive treatment of partial-onset seizures (POS) in adults aged 18 years and older, with subsequent approval as monotherapy.
Interactive Code for Guiding Dose Selection
Assuming a linear one-compartment model for the pharmacokinetics (PK) with and without dose-dependent saturable bioavailability, and a direct inhibitory Emax model for bio-marker effect (PD), develop an...
Pharmacokinetic-Pharmacodynamic Modeling and Simulation to Predict Efficacy Outcomes With Eslicarbazepine Acetate 800 mg Once Daily as Monotherapy for Partial-Onset Seizures
Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED), approved as adjunctive treatment for partial-onset seizures (POS) in the USA, Europe, and Canada, and as monotherapy for POS in the USA.
Providing Insight into Novel Dosing Protocols Using a Quantitative Systems Pharmacology (QSP) Model of Drug-Induced Liver Injury
Elevations in serum alanine aminotransferase (ALT) were observed in phase I clinical studies for a novel inpatient anti-infective therapy (Compound X).
Mechanistic Modeling with Dilisym® Predicts Species Differences in CKA Via Multiple Hepatotoxicity Mechanisms
To predict species differences in CKA-mediated hepatotoxicity using DILIsym®, a mechanistic model of drug-induced liver injury (DILI)
Mechanistic Modeling of Drug-Induced Liver Injury Due to mtDNA Depletion in DILIsym®
To simulate drug-induced liver injury (DILI) due to mitochondrial DNA (mtDNA) depletion in DILIsym using Fialuridine (FIAU) as an exemplar compound.
MembranePlus™: a tool to study in vitro/in vivo transport and drug-drug interaction
MembranePlus (Simulations Plus, Inc.) was used to analyze the concentration-time profiles in donor and receiver compartments after apical and basolateral administration of 50 μg/mL (81.5 μM) indinavir alone...
Physiologically Based Pharmacokinetic (PBPK) Modeling of Amoxicillin in Neonates and Infants
An amoxicillin PBPK model was previously developed and validated in healthy adults as well as adults with altered renal function [1-2]. The purpose of this study was to explore the utility of the model...
Quantitative Estimation Of Predictive Uncertainty
The performance of QSAR models has traditionally been evaluated in terms of aggregate statistics – sensitivity, specificity, root mean square error (RMSE), R2, etc. – for some kind of test set.
Physiologically based pharmacokinetic (PBPK) model for intramuscular injection of aripiprazole
Aripiprazole is an atypical antipsychotics drug that is widely used in the treatment of agitation associated with schizophrenia, schizoaffective disorder, schizophreniform disorder or bipolar I disorder.