Pharmacometric modeling and simulation (M&S) is moving from merely describing pharmacokinetic (PK) and pharmacodynamic (PD) phenomena to informing critical drug development and regulatory decision-making…
Population PK/PD Modeling of Efficacy and Safety of CB1R Inverse Agonist Taranabant in Obese Patients
Taranabant is a cannabinoid-1 receptor (CB1R) inverse agonist, that was being developed by Merck and Co., Inc. as a potential treatment of obesity.
Simulation of Food Effect on Cilostazol Exposure in Human
For certain drugs, the time of administration respective to meal times can have a significant impact on exposure. The effect of food is usually attributed to increased solubility/dissolution rate and/or…
Improving the Efficiency and Ensuring the Quality of Data Assembly for Pharmacometric Analysis
Better tools and processes can improve the efficiency of data assembly and the quality of analysis-ready datasets for pharmacometric analyses.
Modeling and Simulation Approach to Pediatric Drug Development
Describe a process for determining pediatric drug doses using pharmacokinetic/pharmacodynamic (PK/PD) modeling and simulation.
Prediction of Dose-Dependent Intestinal and Liver First Pass Extraction for CYP3A4 Substrates
Cilostazol and midazolam absorption and pharmacokinetics were simulated using GastroPlus™. The program’s Advanced Compartmental and Transit model described the absorption and intestinal metabolism of both…
Physiologically-Based Model for Fluvoxamine Disposition and Prediction of Drug-Drug Interactions
Fluvoxamine absorption and pharmacokinetics were simulated using GastroPlus™. The program’s Advanced Compartmental and Transit model described the absorption; pharmacokinetics was simulated with a…
Prediction of drug -drug interactions for fluconazole using PBPK – a case with concentration-dependent liver:plasma partition coefficient
Fluconazole is an antifungal agent widely used in the clinical setting for the treatment of candidiasis and meningitis. It undergoes minimal metabolism and is excreted renally(1). Fluconazole is a moderate…
Modeling Drug Disposition in Ocular Tissues following Topical Eye Drops and Intravitreal Injection
The purpose of this study was to model the ocular absorption, distribution and clearance of clonidine and voriconazole from topical and intravitreal applications, respectively. Clonidine is a potent…
Development of a Steady-State Exposure-Response Model for Exenatide Once Weekly
Exenatide is dosed as a subcutaneous (SC) injection of 5 and 10 μg twice daily (BID) before main meals and is indicated for the treatment of type 2 diabetes mellitus in patients failing to achieve adequate…
Omeprazole: Physiologically Based Pharmacokinetic (PBPK) Modeling and Prediction of Drug-Drug Interactions (DDI)
To optimize a PBPK model of omeprazole for prediction of DDIs with respect to polymorphic expression of CYP enzymes. Omeprazole absorption and pharmacokinetics were simulated using GastroPlus™.
Azole Antifungals: Physiologically-Based Pharmacokinetic (PBPK) Modeling and Prediction of Drug-Drug Interactions (DDIs)
Develop PBPK models for azole antifungals for prediction of DDIs. The absorption and pharmacokinetics of azole antifungals were simulated using GastroPlus™. The program's Advanced Compartmental and…
Azole Antifungals: Physiologically-Based Pharmacokinetic (PBPK) Modeling and Prediction of Drug-drug Interactions (DDIs)
Download the poster presented at the Rosenon conference in 2009 on the development of PBPK models for common azole antifungals and DDI predictions
Prediction of drug-drug interaction (DDI) between cilostazol and substrates or inhibitors of CYP 2C19 and 3A4
The aim of this study was to validate the utility of physiologically based pharamcokinetic (PBPK) models fore predictioin of DDI between cilostazol, kectoconazole, omeprazole and quindine.
General Approach to Calculation of Tissue:Plasma Partition Coefficients for Physiologically Based Pharmacokinetic (PBPK) Modeling
To conduct a comprehensive evaluation of methods for calculation of tissue/plasma partition coefficients with a focus on correct prediction of volume of distribution and recommendation for a general…
Role of Fraction Unbound in Plasma in Calculations of Tissue:Plasma Partition Coefficients
Previous investigations have shown that the Rodgers and Rowland method [Rodgers 2007] for prediction of tissue:plasma partition coefficients (Kps) provides good prediction for compounds with low to moderate…
Level A IVIVC Using a Comprehensive Absorption/PBPK Model for Metoprolol
Wagner-Nelson, Loo-Riegelman, numerical deconvolution, and convolution-based methods are conventional ways to form an in vitro-in vivo correlation (IVIVC). The ultimate goal for forming an IVIVC is to…
Modeling Effects of Exenatide on the Pharmacokinetics of Acetaminophen, Digoxin, and Warfarin
Exenatide, a 39-amino acid peptide used for treatment of type 2 diabetes, is known to inhibit gastric emptying and as a result to alter the absorption of orally administered concomitant medications.
Mechanistic Modeling of Metoprolol Absorption and Pharmacokinetics from Immediate and Modified Release Formulations
As one of the most widely used b-blocking agents, metoprolol is also a popular drug in research studies. A number of published studies describe the pharmacokinetics as well as the pharmacodynamics of…
PBPK Modeling of Metoprolol and Its Metabolites
Develop a model describing absorption and pharmacokinetics of metoprolol and the formation and pharmacokinetics of its metabolites.