Adinazolam has been reported to have anxiolytic and antidepressant properties [1]. Numerous pharmacokinetic (PK) and pharmacodynamic (PD) studies of immediate release as well as sustained release…
Designing In Vitro Dissolution Tests to Better Mimic In Vivo Release
In vitro dissolution tests were traditionally designed for quality control. USP methods commonly used to evaluate the release rate of new controlled release dosage forms are often based on such experiments.
The Application of Systematic Analysis for Identifying and Addressing the Needs of the Pharmacometric Process
The current implementation of a pharmacometric process has, in most cases, grown from the ad hoc application of modeling and simulation activities to the drug-development process. This ad hoc…
Mechanism-Based Pharmacokinetic / Pharmacodynamic Model for Hepatoprotective Effect of Dexamethasone on Transient Transaminitis After Trabectedin (ET-743, Yondelis®) Treatment
Reversible transient elevations in transaminases have been observed after trabectedin (T) administration, despite no alteration in plasma PK. A PKPD model was developed to evaluate the time course of ALT elevation…
Effect of Lifestyle Intervention on the Placebo Response in Anti-Obesity Trials: Considerations for Exposure-Response Modeling
Successful clinical development of anti-obesity agents is aided by characterization of the placebo effect, which can be significant when lifestyle intervention (LSI) accompanies pharmacologic therapy.
Model-Based Evaluations to Select and Confirm Doses in the Clinical Development of Exenatide
Population pharmacokinetic (PK) and pharmacodynamic (PK/PD) models based on early Phases 1 and 2 data for the new antidiabetic medication exenatide (ex) supported transition from weight-based to…
Population Pharmacokinetics of Paliperidone ER in Healthy Subjects and Patients With Schizophrenia
To develop a population pharmacokinetic (PPK) model for paliperidone extended-release (ER) and to evaluate the influence of selected covariates.
Population Pharmacokinetics of (R)-Albuterol Following Inhaled Levalbuterol or Racemic Albuterol via a Hydrofluoroalkane Metered Dose Inhaler in Pediatric and Adult Asthma Patients
Levalbuterol (LEV), the (R)-enantiomer of racemic albuterol (RA), is approved for the treatment or prevention of bronchospasm in patients ≥4 years of age via metered dose inhaler (MDI). A population…
Population Pharmacokinetics of Nebulized Arformoterol in Subjects with COPD
(R,R)-Formoterol (ARF) is a highly selective, potent and long-acting β2-adrenoceptor agonist currently under development in the US for the longterm maintenance treatment of bronchoconstriction associated…
Exposure-Response Relationship for Nebulized Arformoterol in Subjects with COPD
Arformoterol (ARF) is a highly selective, potent, long-acting β2-adrenoceptor agonist under development in the US for the maintenance treatment of bronchoconstriction associated with COPD. An initial…
Pharmacokinetic/Pharmacodynamic (PK/PD) Model for the Safety of Tigecycline (T) in Patients with Complicated Intra-Abdominal Infections (cIAI)
Nausea (N) and vomiting (V) have been reported with tigecycline, a new glycylcycline with expanded broad spectrum activity. 140 exposure-response relationships and patient covariates predictive of the first N…
Pharmacokinetic/pharmacodynamic (PK/PD) Model for Tolvaptan in Healthy Subjects
Direct effect, indirect effect, and competitive antagonism models were evaluated to describe plasma tolvaptan concentration effect on urine flow rate (UFR), with consideration of water intake rate (WIR)…
Simulation of Midazolam Absorption and Bioavailability in Pediatric Patients
To evaluate the accuracy of prediction of Midazolam absorption and bioavailability in a pediatric population from in silico, in vitro and adult in vivo data. The significance of scaling of the clearance and…
In Vitro Simulation Adinazolam Mesylate Swellable HPMC Matrix Release Using DDDPlus™ Software
Pharmaceutical systems containing a mixture of drug, excipients, and polymer can be used as effective controlled release formulations. The presence of drug and excipients in the polymer matrix creates a…
Population Pharmacokinetics of Tigecycline in Patients with Complicated Skin and Skin-Structure and Intra-Abdominal Infections
Tigecycline is a novel glycylcycline antibiotic with expanded broad-spectrum in vitro activity, including emerging multidrug-resistant pathogens. The goal of this analysis was to develop a PPK model for…
Noncompartmental Pharmacokinetics of Tigecycline in Phase 3 Studies of Patients with Complicated Skin and Skin-Structure and Intra-Abdominal Infections
Tigecycline is the first glycylcycline to reach Phase 3 clinical trials and is active against multidrug-resistant organisms. Four Phase 3 studies have examined tigecycline for the treatment of complicated…
Adult and Pediatric GastroPlus-PBPK Simulations of Gabapentin using in silico Population Estimates for Age-Related (PEAR) Physiology
To evaluate the accuracy of prediction of Midazolam absorption and bioavailability in a pediatric population from in silico, in vitro and adult in vivo data. The significance of scaling of the clearance and…
Population Pharmacokinetics of Tigecycline in Patients with Complicated Intra-abdominal or Skin and Skin-Structure Infections
Tigecycline is a novel glycylcycline antibiotic demonstrating broad-spectrum in vitro activity. A previously developed population pharmacokinetic (PK) model was utilized to generate individual predicted…
Population Pharmacokinetics of Modafinil Film-Coated Tablets in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder
Modafinil is currently being evaluated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. A population pharmacokinetic model was developed…
Pharmacokinetic/Pharmacodynamic Model for the Safety of Tigecycline in Patients with Complicated Skin and Skin-Structure Infections
Tigecycline is a first-in-class glycylcycline for the treatment of serious bacterial infections. Reported adverse events from clinical trials include nausea and vomiting. Exposure-response relationships and…