A predictive, quantitative, mathematical model (DILIsym™) is under development as a public-private initiative based on the physiological processes involved in drug-induced liver injury. The model includes…
Finally, a User-Friendly Way of Computing and Presenting Individual Group Contributions to Polyprotic Ionization of Drugs
It is tempting to “assign” the macroscopic ionization constants (apparent pKa ‘s obtained from titration experiments) of molecules to specific ionizable groups; however, this is strictly appropriate only…
Physiologically-Based Pharmacokinetic (PBPK) Model for Prediction of Midazolam Pharmacokinetics After Intranasal Administration in Children
To predict midazolam absorption and pharmacokinetics (PK) after intranasal (i.n.) administration in young children. The absorption and PK of midazolam were simulated using GastroPlus™. The program’s…
Physiologically-Based Pharmacokinetic (PBPK) Models for Prediction of Saquinavir Effect on Midazolam Pharmacokinetics
Physiologically-based pharmacokinetic (PBPK) models for prediction of saquinavir effect on midazolam pharmacokinetics
Viera Lukacova, Walter S. Woltosz, Michael B. Bolger
Translating Disposition of Sotalol from Healthy Adults to Predict Its Behavior in Pediatric and Adult Subjects with Enhanced and Diminished Renal Clearance
To extend a physiologically based pharmacokinetic (PBPK) model of sotalol developed in healthy adults to predict its behavior in pediatric subjects and adults with varying degrees of renal clearance…
A Pharmacokinetic and Safety Evaluation of Single Oral Doses of Eszopiclone in Pediatric Subjects from 6 to 17 Years of Age with Attention Deficit Hyperactivity Disorder and Insomnia
Eszopiclone is a single-isomer, nonbenzodiazepine, cyclopyrrolone agent that has demonstrated efficacy with both polysomnography (PSG) and patient-reported measures in non-elderly adults with chronic primary…
Grouping Pharmacokinetic Profiles Using Kohonen Self-Organizing Maps
The shapes of plasma concentration versus time (Cp-time) profiles from large clinical trials are often highly variable, even in well-controlled trials involving homogeneous cohorts.
Transporter-Based in vitro-in vivo Extrapolation (IVIVE)
The use of in vitro data to predict the pharmacokinetics (PK) of drugs whose disposition is mediated by transporters is complicated due to unknown transporter expression levels in individual tissues both…
Pharmacokinetic (PK) And Pharmacodynamic (PD) Modeling Of Subcutaneous (Sc) Ly2189102, A Neutralizing IL-1 Beta Antibody, In Patients With Type 2 Diabetes Mellitus
LY2189102, a humanized neutralizing IL-1β antibody, was studied in type 2 diabetes mellitus (T2DM) patients with C-reactive protein (CRP) ≥ 2 mg/L, who received weekly subcutaneous doses of LY2189102…
Simulation of Tobramycin Pharmacokinetics After Topical Ophthalmic Administration
Tobramycin belongs to the class of aminoglycoside antibiotics. It does not bind to serum proteins [1], is eliminated mainly by renal secretion [2] and is poorly absorbed from the gastrointestinal tract [3].
Semi-mechanistic PK/PD Model of the Effect of Odanacatib, a Cathepsin K Inhibitor, on Bone Turnover to Characterize Lumbar Spine and Distal Forearm Bone Mineral Density in a Phase IIb Study of Postmenopausal Women
Odanacatib (MK-0822), a potent, orally-active inhibitor of cathepsin K, is under clinical development for treatment of postmenopausal osteoporosis. This poster describes base model development of a…
Simulating the Disposition of Triamcinolone Acetonide following Oral and Pulmonary Administration
Absorption, distribution and clearance of triamcinolone acetonide (TA) from oral and pulmonary administrations have been simulated using GastroPlus™,1. Simulation of orally administered doses and swallowed…
Mixture Modeling as a Data Imputation Method
To demonstrate the use of mixture modeling in population PK analysis to predict drug concentrations for a subset of subjects with missing data for a key categorical covariate.
A Semi-mechanistic Approach to PK/PD Modeling of Complex Response Data: Bone Turnover Example for Odanacatib, a Cathepsin K Inhibitor
A variety of approaches can be taken to incorporate greater mechanistic understanding into PK/PD models, including a variety of bottom-up, middle-out, and top-down approaches. The osteoporosis field…
New to an Organization: Tools to Assess Projects and Teams
The complexity of project management and its value increase exponentially as the number and complexity of projects and interdisciplinary team participation increases.
Exposure–Response Analysis of Eslicarbazepine Acetate as Adjunctive Treatment of Patients With Partial-onset Seizures
Eslicarbazepine acetate (ESL) is a novel once-daily (QD) antiepileptic drug (AED) currently under clinical development in the US. ESL is rapidly and extensively metabolized to its major active metabolite…
Population Pharmacokinetics of Eslicarbazepine Acetate in Patients With Partial-onset Seizures
Eslicarbazepine acetate (ESL) is a novel once-daily antiepileptic drug (AED) currently under clinical development in the US. Following oral administration, ESL is rapidly and extensively metabolized…
Evolving hERG Inhibition Model
Modeling hERG inhibition has significantly gained popularity since 2005, when the FDA recognized the correlation between hERG inhibition and a prolonged QT interval by issuing guidance for the…
Physiologically-Based Pharmacokinetic (PBPK) Model for Prediction of Tobramycin Pulmonary Absorption and Pharmacokinetics in Children
To fit an absorption-pharmacokinetic model for simulation of tobramycin in adult and pediatric populations. Tobramycin pulmonary absorption and pharmacokinetics were simulated using GastroPlus™.
Physiologically-based pharmacokinetic {PBPK) models for prediction of time-dependent enzyme inhibition (TDI): effect of diltiazem on midazolam and quinidine
Purpose of the study was to optimize a PBPK model to predict timedependent and competitive inhibition of CYP 3A4 by diltiazem...