Precision Criteria to Derive Sample Size When Designing Pediatric Pharmacokinetics Studies: Which Measure of Variability Should be Used?

A new approach for calculation of sample size in pediatric clinical pharmacokinetic studies was suggested based on desired precision for a pharmacokinetic parameter of interest. The estimate of variability for sample size calculations could be obtained from different sources. It is not known whether these sources constantly show higher/lower variability across compounds and age groups. We obtained estimates of variability for clearance, volume of distribution and area under the plasma concentration-time … Continued

Prediction of Overall Survival or Progression Free Survival by Disease Control Rate at Week 8 Is Independent of Ethnicity: Western Versus Chinese Patients with First-line Non-small Cell Lung Cancer Treated with Chemotherapy with or without Bevacizumab

Categorizations of best response observed at week 8 of first-line treatment in two studies of bevacizumab plus chemotherapy in Western and Chinese patients with non-small cell lung cancer were assessed together with baseline prognostic factors in multivariate parametric models to predict overall survival and progression free survival.

Age Related Changes in Fractional Elimination Pathways for Drugs: Assessing the Impact of Variable Ontogeny on Metabolic Drug-drug Interactions

The magnitude of any metabolic drug-drug interactions (DDIs) depends on fractional importance of inhibited pathway which may not necessarily be the same in young children when compared to adults. The ontogeny pattern of cytochrome P450 (CYP) enzymes (CYPs 1A2, 2B6, 2C8, 2C9, 2C18/19, 2D6, 2E1, 3A4) and renal function were analyzed systematically. Bootstrap methodology was … Continued

Do Children Have the Same Vulnerability to Metabolic Drug-drug Interactions as Adults? A Critical Analysis of the Literature

Many drug–drug interactions (DDIs) in the pediatric population are managed based on data generated in adults. However, due to developmental changes in elimination pathways from birth to adolescence, and variable weight-adjusted dose of interacting drugs, the assumption of DDIs being similar in adults and pediatrics might not be correct. This study compares the magnitude of … Continued

Axitinib in Metastatic Renal Cell Carcinoma: Results of a Pharmacokinetic and Pharmacodynamic Analysis

Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, approved for second-line therapy for advanced renal cell carcinoma (RCC). Axitinib population pharmacokinetic and pharmacokinetic/pharmacodynamic relationships were evaluated. Using nonlinear mixed effects modeling with pooled data from 383 healthy volunteers, 181 patients with metastatic RCC, and 26 patients … Continued

Race and Drug Formulation Influence on Mycophenolic Acid Pharmacokinetics in Stable Renal Transplant Recipients

Limited mycophenolic acid (MPA) data are available comparing racial influence on mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) pharmacokinetics. Intrapatient MPA pharmacokinetics of MMF versus EC-MPS were compared in 13 male African American (AA) and 14 Caucasian (C) renal transplant recipients (RTRs). RTRs were switched to equivalent doses of the alternate formulation for at … Continued

Inhibitory Effect of Ketoconazole on the Pharmacokinetics of a Multireceptor Tyrosine Kinase Inhibitor BMS-690514 in Healthy Participants: Assessing the Mechanism of the Interaction with Physiologically-based Pharmacokinetic Simulations

BMS-690514, a selective inhibitor of the ErbB and vascular endothelial growth factor receptors, has shown antitumor activity in early clinical development. The compound is metabolized by multiple enzymes, with CYP3A4 responsible for the largest fraction (34%) of metabolism. It is also a substrate of P-glycoprotein (P-gp) in vitro. To assess the effect of ketoconazole on … Continued

Armodafinil and Modafinil in Patients with Excessive Sleepiness Associated with Shift Work Disorder: A Pharmacokinetic and Pharmacodynamic Model for Predicting and Comparing Their Concentration-effect Relationships

Armodafinil, the longer lasting R-isomer of racemic modafinil, improves wakefulness in patients with excessive sleepiness associated with shift work disorder (SWD). Pharmacokinetic studies suggest that armodafinil achieves higher plasma concentrations than modafinil late in a dose interval following equal oral doses.

Population Pharmacokinetics of Vernakalant Hydrochloride Injection (RSD1235) in Patients with Atrial Fibrillation or Atrial Flutter

Vernakalant hydrochloride is a novel, predominantly atrial-selective antiarrhythmic drug that effectively and rapidly terminates atrial fibrillation (AF). Plasma vernakalant concentration data from 5 phase 2 and 3 clinical trials of vernakalant in patients with AF or atrial flutter and a phase 1 study in healthy volunteers were used to construct a population pharmacokinetic model

Population Pharmacokinetic Model for a Novel Oral Hypoglycemic Formed In Vivo: Comparing the Use of Active Metabolite Data Alone Versus Using Data of Upstream and Downstream Metabolites

The purpose of this analysis was to develop a population pharmacokinetic model for CS-917, an oral hypoglycemic prodrug, and its 3 metabolites. The population pharmacokinetic model was used to predict exposure of the active moiety R-125338 and thus to identify potential CS-917 dosage reduction criteria.

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