Biopreservation and reversal of oxidative injury during blood storage by a novel curcumin-based gel formulation.

Blood storage lesion induces cytosolic and membrane changes driven in part by hemoglobin (Hb) oxidation reactions within red blood cells (RBCs). A novel gel formulation containing the antioxidant curcuminoids in a biocompatible solvent system was used to deliver curcumin into RBCs. Incubation of peroxide treated RBCs stored in PBS with curcumin gel led to a reduction in prooxidant ferrylHb and recovery in ATP.

Racial and Ethnic Representation in US Clinical Trials of New Drugs and Biologics, 2015-2019.

This study reviews the participation of racial and ethnic populations at US sites in 2015-2019 to understand the extent to which US trial participation represents the diversity of the US population.

U.S. racial and ethnic participation in global clinical trials by therapeutic areas.

What Is Known And Objective: The discussion about health equity in the United States frequently involves concerns over racial and ethnic minority under-representation in clinical trials and particularly in trials conducted in support of product approvals. The FDA has long worked to encourage diverse participation in clinical trials and through its Drug Trials Snapshots (DTS) program, the U.S.

Engineering T cells to enhance 3D migration through structurally and mechanically complex tumor microenvironments.

Defining the principles of T cell migration in structurally and mechanically complex tumor microenvironments is critical to understanding escape from antitumor immunity and optimizing T cell-related therapeutic strategies. Here, we engineered nanotextured elastic platforms to study and enhance T cell migration through complex microenvironments and define how the balance between contractility localization-dependent T cell phenotypes influences migration in response to tumor-mimetic structural and mechanical cues. Using these platforms, we characterize a mechanical optimum for migration that can be perturbed by manipulating an axis between microtubule stability and force generation.

Weighty choices: selecting optimal G-CSF doses for stem cell mobilization to optimize yield.

There are limited data on the effect of donor body mass index (BMI) on peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF), especially in unrelated donors. Obesity has been associated with persistent leukocytosis, elevated circulating progenitor cells, and enhanced stem cell mobilization. Therefore, we hypothesized that adequate collection of CD34+ cells may be achieved with lower doses (per kilogram of body weight) of G-CSF in donors with higher BMI compared with donors with lower BMI.

Diagnosis-based cohort augmentation using laboratory results data: The case of chronic kidney disease.

Purpose: In this report, we use data from FDA's Sentinel System to focus on how augmenting a diagnosis-based chronic kidney disease cohort with patients identified through laboratory results impacts cohort characteristics and outcomes.

Methods: We used data from 2 Data Partners. Patients were eligible if they were health plan members on January 1, 2012.

Comparison of Detection Limits of Fourth- and Fifth-Generation Combination HIV Antigen-Antibody, p24 Antigen, and Viral Load Assays on Diverse HIV Isolates.

Detection of acute HIV infection is critical for HIV public health and diagnostics. Clinical fourth-generation antigen (Ag)/antibody (Ab) combination (combo) and p24 Ag immunoassays have enhanced detection of acute infection compared to Ab-alone assays but require ongoing evaluation with currently circulating diverse subtypes. Genetically and geographically diverse HIV clinical isolates were used to assess clinical HIV diagnostic, blood screening, and next-generation assays.

Prediction of Tissue to Plasma Concentration Ratios of Drugs in the Rat from Experimentally Estimated Volume of Distribution: Application of Allometry.

Background: In Physiologically Based Pharmacokinetic (PBPK) models, the most important input parameter is tissue-to-plasma partition coefficient (Kp). Over the years, several empirical methods have been developed to predict Kp in animals.

Objectives: The objective of this study was to propose two allometric methods to predict Kp from experimentally determined in vivo volume of distribution at steady state (Vss).

Prediction of Plasma Concentration-time Profiles of Drugs in Humans from Animals Following Oral Administration: An Allometric Approach.

Background: Allometric scaling is regularly used for the prediction of human pharmacokinetic (PK) parameters from animal PK studies. The predicted human PK parameters can also be used for the prediction of plasma concentration-time profiles in humans.

Objectives: The main objective of this work is to predict human concentration-time profiles of drugs (one-compartment model) following oral administration using animal oral pharmacokinetic parameters.

Prediction of Clearance in Neonates and Infants (≤ 3 Months of Age) for Drugs That Are Glucuronidated: A Comparative Study Between Allometric Scaling and Physiologically Based Pharmacokinetic Modeling.

The objective of this study was to evaluate the predictive performances of allometric models and a physiologically based pharmacokinetic model (PBPK) to predict clearance of glucuronidated drugs in neonates (≤ 3 months of age). From the literature, clearance values for 9 drugs (glucuronidated) for neonates and adults were obtained. Three allometric models were used to predict clearances of these glucuronidated drugs.

Prediction of Clearance and Dose of Midazolam in Preterm and Term Neonates: A Comparative Study Between Allometric Scaling and Physiologically Based Pharmacokinetic Modeling.

Children are not small adults because besides size there are subtle physiological and biochemical differences between children and adults. Like adults, children also require medicine for the management or cure for the underlying diseases. To select a right dose in children, pharmacokinetic (PK) information is warranted.

Prediction of Clearance, Volume of distribution, and Half-life of Drugs in Extremely Low to Low Birth Weight Neonates: An Allometric Approach.

Background And Objectives: More than 20 million infants worldwide (15.5 % of all births) are born with low birth weight. Low birth weight is associated with poor growth in childhood and a higher incidence of adult diseases, such as type 2 diabetes, hypertension and cardiovascular disease.

Pharmacokinetic Considerations in Designing Pediatric Studies of Proteins, Antibodies, and Plasma-Derived Products.

Ignoring the principles of pediatric pharmacology can have serious consequences. Therefore, it is necessary to understand and recognize the impact of developmental processes in children. It is now well recognized that age and the disease state can alter the pharmacokinetics (PKs) of a drug, as a result adjustment in dosing regimen in children as compared with the adults is essential.

Prediction of Human Glomerular Filtration Rate from Preterm Neonates to Adults: Evaluation of Predictive Performance of Several Empirical Models.

The objective of this study was to evaluate the predictive performance of several allometric empirical models (body weight dependent, age dependent, fixed exponent 0.75, a data-dependent single exponent, and maturation models) to predict glomerular filtration rate (GFR) in preterm and term neonates, infants, children, and adults without any renal disease. In this analysis, the models were developed from GFR data obtained from inulin clearance (preterm neonates to adults; n = 93) and the predictive performance of these models were evaluated in 335 subjects (preterm neonates to adults).

Prediction of Drug Clearance in Premature and Mature Neonates, Infants, and Children ≤2 Years of Age: A Comparison of the Predictive Performance of 4 Allometric Models.

The objective of this study was to evaluate the predictive performance of 4 allometric models to predict clearance in pediatric ages ranging from premature neonates to children ≤2 years of age. Four allometric models were used to predict clearances of 28 drugs in children from preterm neonates to 2 years of age (n = 564). The 4 models are (1) basal metabolic rate-dependent model; (2) age-dependent exponent model; (3) an allometric model based on kidney and liver weights as well as kidney and liver blood flow; and (4) an allometric model based on a fixed exponent of 0.

Flow cytometry evaluation of in vitro cellular necrosis and apoptosis induced by silver nanoparticles.

Particles possess unique properties in the nanoscale, e.g., enhanced catalytic activity, high surface area, and light emission/absorption properties, that might result in interference with colorimetric in vitro cytotoxicity assays such as MTT, XTT or MTS.

Prediction of drug clearance in children: a review of different methodologies.

Introduction: Children are not small adults because the differences between adults and children are not simply due to body weight, but also due to physiological and biochemical differences. Hence, dosing in children should not be a 'small adult dose'. During pediatric drug development, selection of a suitable dose for the first-in-children clinical study (Pharmacokinetic [PK], safety and efficacy) is of utmost importance.

Joint Estimation of Treatment and Placebo Effects in Clinical Trials with Longitudinal Blinding Assessments.

In some therapeutic areas, treatment evaluation is frequently complicated by a possible placebo effect (i.e., the psychobiological effect of a patient's knowledge or belief of being treated).

Prediction of drug clearance in children: an evaluation of the predictive performance of several models.

The objective of this study is to evaluate the predictive performance of several models to predict drug clearance in children ≤5 years of age. Six models (allometric model (data-dependent exponent), fixed exponent of 0.75 model, maturation model, body weight-dependent model, segmented allometric model, and age-dependent exponent model) were evaluated in this study.

Vertical allometry: fact or fiction?

In pharmacokinetics, vertical allometry is referred to the clearance of a drug when the predicted human clearance is substantially higher than the observed human clearance. Vertical allometry was initially reported for diazepam based on a 33-fold higher human predicted clearance than the observed human clearance. In recent years, it has been found that many other drugs besides diazepam, can be classified as drugs which exhibit vertical allometry.

Prediction of glucuronidated drug clearance in pediatrics (≤5 years): An allometric approach.

Children are not small adults. The differences between children of different age groups and adults are not merely due to body weight, but also due to physiological and biochemical differences resulting in different rates of drug metabolism or renal clearance. Glucuronidation is an important pathway of drug metabolism.

Dosing in children: a critical review of the pharmacokinetic allometric scaling and modelling approaches in paediatric drug development and clinical settings.

It should be recognized that children are not small adults, hence dosing in children should not be a 'small adult dose'. A mean population dose in all age groups is just an average dose and not necessarily the best or the correct dose for a given patient. The dose of a drug varies from patient to patient and individual adjustment of the dose is always ideal but is not always practical.

Designing first-in-human dose of coagulation factors: application of pharmacokinetic allometric scaling.

The objectives of this study were to (i) evaluate the predictive performance of pharmacokinetic interspecies scaling of coagulation factors to predict clearance (CL) and (ii) project first-in-human dose based on the predicted human CL. Human CL of nine coagulation factors was predicted using two or three animal species using two methods: (i) CL vs. body weight (simple allometry) and where applicable (ii) the product of CL and brain weight vs.

Prediction of drug concentration-time profiles in children from adults: an allometric approach.

The main objective of this work was to evaluate 2 methods to predict concentration-time profiles of drugs in children (aged 5 years or older) from adult pharmacokinetic (PK) parameters. Five drugs from the literature were chosen for this study, and all these 5 drugs were described by a 2-compartment model in both adults and children. PK parameters (CL, Vc, Vss, and Vβ) were allometrically predicted in children from adults.