Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) approved by the US Food and Drug Administration for the treatment of partial-onset seizures (POS) as monotherapy or…
Prediction of Oral Bioavailability in silico
A database of 62 drugs including oral bioavailability (F%) and dose was constructed: All compounds’ reported major clearance pathways (MCP) were CYP-mediated, For 43 drugs with more than one reported value...
Toward Progressive Reporting of Modeling and Simulation Results – Part 1: Analysis of KIWI™ Metadata
Technical reports for pharmacometric modeling provide comprehensive documentation, typically including data assembly methods and disposition, modeling strategy, and analysis results. These reports, however…
Determination of Susceptibility Breakpoints for the Novel Oxazolidinone Tedizolid
Tedizolid is a novel oxazolidinone antibacterial with potent in vitro activity against a wide range of Gram-positive pathogens, such as Staphylococcus aureus (including methicillin-resistant S. aureus)...
In Silico Modeling Can Predict the Unforeseen Renal Failure Caused by SGX523, a c-MET Kinase Inhibitor
SGX523 is a quinoline containing,c-MET kinase inhibitor with an IC50 of 4nM (BuchananSGetal.,2009): Inhibited thegrowth of human glioblastoma lung and gastric cancer xenografts in mice, in a Phase 1 clinical...
Predicting Five Rat Acute Toxicity Endpoints with ANNE Models using ADMET Predictor™
Alternative methods are being explored to predict the toxicity of chemicals to reduce use of animals. Laboratory/Animal tests are costly in time and money, Cheminformatics (QSTR) presents a good alternative to…
Fluorometholone Ocular Suspension PBPK Simulations Using the OCAT™ Model in GastroPlus™
Development of generic formulations of ophthalmic corticosteroids and regulatory acceptance of bioequivalence can be facilitated by analysis of the mechanisms of ocular dissolution, absorption...
A Population-Based PK/PD Analysis Of Dasotraline Efficacy In The Treatment Of ADHD In Adults
Dasotraline (SEP-225289) is a new chemical entity with a slow elimination half-life demonstrating dopamine (DAT) and norepinephrine (NET) transporter inhibition in clinical studies. Here we hypothesized…
Eslicarbazepine Acetate Drug–Drug Interactions: Characterization Through a Model-Based Population Approach
Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED), approved by the US Food and Drug Administration for the treatment of partial-onset seizures (POS) as monotherapy or...
Eslicarbazepine Acetate Monotherapy: A Population Ppharmacokinetic Analysis
Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED), approved by the US Food and Drug Administration for the treatment of partial-onset seizures (POS) as monotherapy or…
Relationship between exposure and efficacy of eslicarbazepine acetate monotherapy
Eslicarbazepine acetate (ESL) is a once-daily, oral antiepileptic drug (AED), approved by the US Food and Drug Administration for the treatment of partialonset seizures (POS) as monotherapy or adjunctive...
Relationship Between Eslicarbazepine Exposure and Efficacy of Eslicarbazepine Acetate Adjunctive Therapy
Eslicarbazepine acetate (ESL; Aptiom®) is a novel once-daily (QD) oral antiepileptic drug, approved in then US, Canada and the EU as adjunctive treatment of partial-onset seizures (POS). ESL is extensively...
Relationship Between Eslicarbazepine Exposure and Safety Endpoints for Eslicarbazepine Acetate Adjunctive Therapy
Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED), approved in the US, Canada and the EU as adjunctive treatment of partial-onset seizures (POS). After oral administration, ESL...
Relationship Between Eslicarbazepine Exposure and Safety Endpoints for Eslicarbazepine Acetate Monotherapy
In two Phase III trials (093-045 and -046) of eslicarbazepine acetate (ESL) monotherapy in patients with partial-onset seizures (POS) uncontrolled by 1−2 antiepileptic drugs (AEDs), the incidence of...
Novel Physiologically-Based Oral Cavity Model and Its Application for Projection of Clinical Pharmacokinetics of Intermezzo® Sublingual Tablets
Intraoral (IO) delivery refers to an alternative administration route that intends to deliver the drug substance through oral mucosa. The intraoral route provides several advantages over conventional...
Prediction of Acyclovir Pharmacokinetics in Pediatric Populations using a Physiologically Based Pharmacokinetic (PBPK) Model
To develop a PBPK model for acyclovir incorporating processes affecting the drug's absorption and distribution after i.v. administration of acyclovir (ACV) as well as its in vivo formation after p.o. admin…
Mechanistic Nucleation and Growth Can Predict Nonlinear Dose-Dependent Precipitation of Enabled Fomulations of Nimodipine in GastroPlus™
Simulation of precipitation can be important for accurate prediction of the absorption of many oral formulations. Amorphous solid dispersions, salt forms, cocrystals, solutions, and nanoparticles all can…
Physiologically Based Pharmacokinetic Modeling of Buspirone and the Effect of Liver Cirrhosis on Its Deposition
The aim of this work was to develop a physiologically based pharmacokinetic (PBPK) model of buspirone following oral administrations in healthy volunteers, and to extend this model to predict the…
Novel Skin PBPK model in Action: Clindamycin and Tazarotene Modeling
Skin is the major organ in the human body with a complex barrier that serves as protection from the external environment. Predicting dermal and systemic exposures of drug following topical application...
Population Modeling Is a Critical Element of Bridging Pharmacokinetic Data From Dried Blood Spot and Plasma Across Clinical Programs
To demonstrate through two case studies how population pharmacokinetic (PK) modeling should be leveraged for bridging plasma and dried blood spot (DBS) PK data across clinical development programs.