A5000728724- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Protein purification and stability
- Prenatal Substance Exposure Effects
- Chronic Lymphocytic Leukemia Research
- Computational Drug Discovery Methods
- Statistical Methods and Bayesian Inference
- Statistical Methods in Clinical Trials
- T-cell and B-cell Immunology
- HER2/EGFR in Cancer Research
- Drug Transport and Resistance Mechanisms
- Neutropenia and Cancer Infections
- Analytical Methods in Pharmaceuticals
- Lung Cancer Research Studies
- Pharmaceutical studies and practices
- Analytical Chemistry and Chromatography
- Cell Adhesion Molecules Research
- Systemic Lupus Erythematosus Research
- Blood disorders and treatments
- Opioid Use Disorder Treatment
- MRI in cancer diagnosis
- Pharmacogenetics and Drug Metabolism
- Neonatal Health and Biochemistry
- Cancer, Hypoxia, and Metabolism
- Pharmacological Effects and Toxicity Studies
National Library Board
2022-2023
University of Kentucky
2016-2021
Markey Cancer Center
2019
National Cancer Institute
2019
Children's Hospital of Philadelphia
2010-2015
University of Pennsylvania
2012-2015
University of Michigan
2014
University of North Carolina at Chapel Hill
1998-2013
California University of Pennsylvania
2013
The University of Texas Health Science Center at San Antonio
2008-2009
Rituximab is a B cell‐depleting anti‐CD20 chimeric IgGK monoclonal antibody being investigated for the treatment of rheumatoid arthritis. The purpose this study was to develop population pharmacokinetic model in arthritis patients. In addition, final used assess variability drug exposure (AUC 0‐∞ ) fixed versus body surface area‐based dosing. A total 102 patients were included analysis. 2‐compartment described data reasonably well. Body area and gender most significant covariates both CL Vc....
This study aimed to assess the safety and feasibility of administering volociximab, a chimeric monoclonal antibody that specifically binds alpha(5)beta(1) integrin, determine pharmacokinetics, pharmacodynamics, preliminary evidence antitumor activity.Patients with advanced solid malignancies were treated escalating doses volociximab i.v. administered over 60 minutes. Blood samples assayed plasma pharmacokinetic parameters, detect human antichimeric formation, saturation alpha5beta1 sites on...
Tacrolimus is used clinically for the long-term treatment of antirejection transplanted organs in liver and kidney transplant recipients, although dose optimization poorly managed. The aim this study was to examine association between tacrolimus pharmacokinetic variability CYP3A4 CYP3A5 genotypes by a population analysis based on routine drug monitoring data adult renal recipients.Trough concentrations were obtained from 161 recipients after transplantation. carried out using nonlinear...
Organic cation transporters (OCTs) are members of the solute carrier 22 family transporter proteins that involved in absorption, distribution, and excretion organic cations. OCT3 is localized apical (AP) membrane enterocytes, but literature ambiguous about OCT1 (mOct1) localization, with some evidence suggesting a basolateral (BL) localization human mouse enterocytes. This contrary to our preliminary findings showing AP Caco-2 cell monolayers, an established model intestinal epithelium....
Chimeric antigen receptor T-cell (CART) therapy is a new and promising cancer therapy. However, severe toxicity due to cytokine release syndrome (CRS) in CART-treated patients highlighted the possible danger of this Disease burden CART doses are potential factors associated with CRS but detail relationships between these severity remain largely unknown. In study, quantitative systems pharmacology (QSP) approach used quantify complex among doses, disease burden, pro inflammatory cytokines...
Objective: Immunoglobulin M (IgM) antibodies have either 10 (pentamer) or 12 (hexamer) antigen binding domains and this avidity renders them highly efficient at antigens present low levels. Recently several engineered IgM been explored as therapeutics for various diseases in clinical trials. However, unlike IgG, is not subjected to FcRn-mediated recycling large size of may limit its tissue distribution. Therefore, there great interest better understand disposition optimizing efficacy...
OBJECTIVE: Development of optimal covariate model for population data analysis is time-consuming, labor-intensive, and nontrivial process. Among many different approaches used to develop models, stepwise selection method (SCM) with forward selection/backward elimination (FS/BE) most commonly in pharmacokinetic/pharmacodynamic (PPK/PD) analysis. Although this standard can reduce number models be tested, it still time-consuming labor-intensive when testing complex long run times. Hence, aim...
Abstract Purpose: To characterize the pharmacokinetics and pharmacodynamics of oxaliplatin in cancer patients with impaired renal function. Experimental Design: Thirty-four were stratified by 24-h urinary creatinine clearance (CrCL) into four dysfunction groups: group A (control, CrCL, ≥60 mL/min), B (mild, 40-59 C (moderate, 20-39 D (severe, <20 mL/min). Patients treated 60 to 130 mg/m2 infused over 2 h every 3 weeks. Pharmacokinetic monitoring platinum plasma, plasma ultrafiltrates,...
Phenobarbital is the first-line treatment for neonatal seizures. Many neonates with hypoxic ischemic encephalopathy are treated therapeutic hypothermia, and about 40% have clinical Little known pharmacokinetics of phenobarbital in infants who undergo hypothermia. The objective this study was to determine effect hypothermia on pharmacokinetics, taking into account maturational changes.Level 3 ICU.Infants suspected seizures, all phenobarbital. Some these also received hypothermia.None.A...
One of the challenges in translational medicine is to select first‐in‐human doses investigational drugs based on findings preclinical studies. Despite substantial progress optimization recombinant adeno‐associated virus (AAV) vectors vivo gene therapy for treating various diseases, there remain significant limitations use data guide dose selection clinical trials. Here we introduce a novel concept efficiency factor (GEF) describe transfer system and apply GEF AAV‐mediated systems. We explore...
Objective Neonatal abstinence syndrome ( NAS )—a clinical entity of infants from in utero exposure to psychoactive xenobiotic and buprenorphine—has been successfully used treat . However, nothing is known about the pharmacokinetics PK ) buprenorphine neonates with To our knowledge, this first study investigate population pharmacokinetic sublingual Design A retrospective analysis of: (1) treated randomized, double blinded (2) data healthy adults a previously published study. Setting intensive...
Neonatal abstinence syndrome (NAS) is a condition affecting newborns that are exposed to an opioid in utero. In randomized, controlled trial assessing the efficacy of buprenorphine and morphine NAS, blood samples were analyzed from subset patients receiving along with NAS scores. The data used validate adapt existing model neonates identify relationships between or norbuprenorphine pharmacokinetics (PK) safety. time stabilization was found decrease increasing exposure. This...
The aim of this study was to investigate neonatal Fc receptor (FcRn) concentration developmental pharmacology in adult and pediatric subjects using minimal physiologically-based pharmacokinetic (mPBPK) modelling. Three types (PK) data for three agents (endogenous/exogenous native IgG, bevacizumab palivizumab) were used. group contained six with weights from 50 100 kg. For subjects, seven age groups assumed, five each having the weight 95%, 75%, 50%, 25% 5% percentile population. A first...
Combination chemotherapy is increasingly practiced for the treatment of malignant prostate cancers. The aim this study was to evaluate in vivo efficacy combined tamoxifen and quercetin tumor xenografts. Severe immune deficient (SCID) mice inoculated with CWR22 cells were treated either (10 mg/kg/week), (200 mg/kg/day) or tamoxifen-quercetin 28 days. Tamoxifen alone exhibited a moderate antitumor activity. decreased Ki-67 index by 52.4%, reduced vascular endothelial growth factor (VEGF) 121...
3590 Background: Insulin-like growth factor receptor (IGF-1R) is a tyrosine kinase cell surface overexpressed in cancer cells which mediates the mitogenic and anti-apoptotic actions of IGF, playing key role malignant transformation. The safety pharmacokinetics 3-weekly administration R1507, human monoclonal antibody selective for IGF-1R, were explored this phase I dose escalation study patients with advanced solid tumors or lymphomas. Materials Methods: Multiple ascending doses R1507...
<title>Abstract</title> Pharmacokinetics and pharmacodynamics of many biologics are influenced by their complex binding to biologic receptor. Biologics consist diverse groups molecules with different kinetics its biological receptors including IgG simple one-to-one drug receptor bindings, bispecific antibody (BsAb) that binds two receptors, can bind six or more receptors. As process is much faster than elimination distribution processes quasi-equilibrium (QE) models commonly used describe...
The secretory transport of the H(2)-antagonists, ranitidine and famotidine, across Caco-2 cell monolayers was found to be a saturable process. Both drugs exhibited greater permeability in basolateral (BL) apical (AP) direction than AP BL direction, indicating apically directed secretion; inhibited by P-glycoprotein (P-gp) inhibitors verapamil cyclosporin A. cellular uptake membrane temperature dependent, indicative carrier-mediated transport. K(m) V(max) for process were estimated 66.9 mM...