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.
Systems Pharmacology Modeling Predicts Hepatotoxic Potential Of Troglitazone And Pioglitazone
Troglitazone (TGZ) caused life-threatening drug-induced liver injury (DILI) in diabetic patients, whereas the next in class, pioglitazone (PGZ), has rarely been associated with DILI. Inhibition of bile acid...
Computational models for improved estimation of highly plasma-protein-bound compounds
Plasma protein binding is an important parameter for characterizing the pharmacokinetics of drug candidates.
KIWI: A Collaborative Platform for Modeling and Simulation
Drug development programs rely increasingly on pharmacometric analysis to support decision-making and submissions to regulatory agencies.1,2 To ensure high quality analysis, organizations must apply…
Tedizolid Plasma Pharmacokinetics Are Comparable in Obese and Nonobese Patients and Healthy Subjects
Tedizolid phosphate is a novel oxazolidinone prodrug antibacterial being investigated for the treatment of Gram-positive infections, including those caused by methicillin-resistant Staphylococcus aureus.
Impact of Delayed-Dose Administration of USL255, Qudexy™ XR (Topiramate) Extended-Release Capsules
Despite the importance of medication adherence for successful management of seizure disorders, nonadherence continues to be a significant problem in patients with epilepsy.
Computational Modeling of OATP1B1 Inhibitors
This poster was presented at the 2014 SOT meeting. It describes where the OATP1b1 data originated and the cutoff value. The model, including descriptors, is discussed.
Quantitative Modeling Uncovers a Potential Limitation in the Putative Mechanism of CCl4 Hepatotoxicity
Drug-induced liver injury (DILI) is one of the leading causes of drug development failures and drug withdrawals. DILIsym® is being developed to identify and mitigate DILI risk through in silico…
Where top-down meets bottom-up: Combined population PK (PopPk) and PBPK approaches to evaluate the impact of food and gastric pH on the pharmacokinetics of GDC-0941
The phosphoinositide 3-kinase (P13K) signaling pathway is deregulated in a wide variety of cancers. GDC-0941 is a potent and selective pan-inhibitor of class I P13K.
Population Pharmacokinetic Evaluation of Eslicarbazepine Acetate for Adjunctive Therapy in Refractory Partial Onset Seizures
Eslicarbazepine acetate (ESL), a once-daily antiepileptic drug (AED), is converted to eslicarbazepine, the primary active metabolite of ESL, after oral administration. The population pharmacokinetics (PK)…
Design, Synthesis, and in vitro Testing of Novel COX-2/COX-1 Inhibitors
To design,synthesize,and test new lead molecules that inhibit both COX-1 and COX-2 forms of the cyclooxygenase (COX) enzyme, with higher affinity for COX-2 than for COX-1.
Prediction of Valsartan Pharmacokinetics in Pediatric Population using Physiologically Based Pharmacokinetic (PBPK) Model
A method for transporter-based in vitro-in vivo extrapolation (IVIVE) was previously developed and demonstrated by predicting valsartan PK after i.v.administration [1]. The purpose of this study was to…
MembranePlus™: A Tool to Study in vitro/in vivo Transport and Drug-Drug Interaction
To develop a mechanistic mathematical model for analysis of in vitro permeability assays that accounts for all mechanisms contributing to observed apparent permeability: passive paracellular and…
Simulating the Disposition of Budesonide from Dry Powder Inhalers (DPIs) and Nebulizers
Objective: To simulate and predict the absorption and pharmacokinetics (PK) of budesonide following orally‐inhaled (OIN) i.e. respiratory administration across multiple formulations and/or devices.