A5025684638- Monoclonal and Polyclonal Antibodies Research
- Lymphoma Diagnosis and Treatment
- Glaucoma and retinal disorders
- CAR-T cell therapy research
- Retinal Development and Disorders
- Receptor Mechanisms and Signaling
- Retinal Diseases and Treatments
- Corneal surgery and disorders
- Drug Transport and Resistance Mechanisms
- Biosimilars and Bioanalytical Methods
- PI3K/AKT/mTOR signaling in cancer
- HER2/EGFR in Cancer Research
- Protein purification and stability
- Diabetes Treatment and Management
- Spinal Dysraphism and Malformations
- Ocular Surface and Contact Lens
- Amyotrophic Lateral Sclerosis Research
- Retinal Imaging and Analysis
- Inflammatory mediators and NSAID effects
- Hepatitis C virus research
- Ophthalmology and Eye Disorders
- Neuroendocrine Tumor Research Advances
- Advanced Drug Delivery Systems
- Acute Lymphoblastic Leukemia research
- Lipid Membrane Structure and Behavior
AbbVie (United States)
2021-2022
Allergan (United States)
2020-2022
Ionis Pharmaceuticals (United States)
2015-2017
Pfizer (United States)
2009-2016
Ghent University Hospital
2013
Fox Chase Cancer Center
2013
St Bartholomew's Hospital
2013
University of the Pacific
2005
Purpose Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, potent cytotoxic agent. We performed phase I/II study determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics INO plus rituximab (R-INO) for treatment relapsed/refractory CD20 + /CD22 B-cell non-Hodgkin lymphoma (NHL). Patients Methods A dose-escalation MTD R-INO was followed by expanded cohort further evaluate...
In the drug discovery and development setting, ability to accurately predict human pharmacokinetics (PK) of a candidate compound from preclinical data is critical for informing effective design first-in-human trial. PK prediction especially challenging monoclonal antibodies exhibiting nonlinear attributed target-mediated disposition (TMDD). Here, we present model-based method predicting PF-03446962, an IgG2 antibody directed against ALK1 (activin receptor-like kinase 1) receptor. Systems...
Nusinersen is an antisense oligonucleotide intended for the treatment of spinal muscular atrophy. The pharmacokinetics nusinersen, following intrathecal administrations, in cerebrospinal fluid (CSF) and plasma 72 pediatric patients (3 months to 17 years) with atrophy across 5 clinical trials was analyzed via population-based modeling. With sparse data CSF profile plasma, a linear 4-compartment model simultaneously described time-concentration profiles both matrices. typical population...
Brimonidine, a selective <i>α</i><sub>2</sub>-adrenoceptor agonist, displays putative retinal cyto- and neuroprotective activity in vitro vivo. An intravitreal sustained-release brimonidine implant, Brimonidine Posterior Segment Drug Delivery System (brimonidine DDS), allowing targeted drug delivery to the retina has been developed for potential clinical application. This study evaluates vivo posterior segment pharmacokinetics of DDS implant monkey eye applies translational pharmacokinetic...
The pharmacokinetics of [(14)C]viramidine, a prodrug ribavirin, were studied in rats (30 mg/kg body weight) and monkeys (10 mg/kg) following intravenous (i.v.) oral administration. levels absorption bioavailabilities 61.7 9.91%, respectively, 43.9 13.6%, monkeys. Following i.v. administration, the elimination half-lives 2.7 h 28.9 Total clearances 14.0 liters/h/kg 1.23 monkeys; apparent volumes distribution 15.6 liters/kg 18.6 viramidine was extensively converted to followed by further...
Abicipar pegol (abicipar) is a novel DARPin therapeutic and highly potent vascular endothelial growth factor (VEGF) inhibitor intended for the treatment of neovascular age-related macular degeneration (nAMD). Here we develop translational pharmacokinetic/pharmacodynamic (PK/PD) model abicipar to guide dosing regimens in clinic. The incorporated abicipar-VEGF binding kinetics, VEGF expression levels, turnover rates describe ocular systemic PK data collected from vitreous, aqueous humor (AH),...
Developing a population-based pharmacokinetic-pharmacodynamic (PKPD) model is challenge in ophthalmology due to the difficulty of obtaining adequate pharmacokinetic (PK) samples from ocular tissues inform pharmacodynamic (PD) model. Using limited PK data, we developed preclinical PD suitable for capturing time course dog intraocular pressure (IOP) that exhibited time-dependent sensitization after topical administration PF-04475270...
Abstract Background: INO (CMC-544) is a novel antibody-drug conjugate composed of CD22-directed IgG4 antibody linked to calicheamicin, potent cytotoxin. In this phase II study, was administered 1.8 mg/m2 intravenously once every 28 days for planned 4 8 cycles patients with indolent B-cell NHL who were refractory rituximab. Objective: The aim analysis evaluate the antitumor activity by performing PK-PD modeling concentrations and tumor size (as determined from sum products diameters)....
Abstract Purpose This study aimed to develop a quantitative method for optimizing the dose and regimen of inotuzumab ozogamicin (InO) in patients with indolent non-Hodgkin lymphoma (NHL) by simultaneously balancing safety efficacy outcome measures Design Analysis was based on data from multi-center, single arm, open-label intravenous InO administered at 1.8 mg/m2, every 4 weeks (Q4W) least cycles. Patients Methods Pharmacokinetics (PK), safety, phase 2 trial 81 were evaluated modeling...
Abstract The PI3K pathway, which regulates cell growth, proliferation and survival, is activated in many types of human tumors by mutational activation PI3Kα, loss function PTEN or receptor tyrosine kinases. Inhibition key signaling proteins the such as PI3K, AKT mTOR, therefore represents a high value targeting strategy for diverse cancers. PF-04691502 dual-specificity inhibitor mTOR shows potent selective activity vitro biochemical, xenograft models. In biochemical assays inhibited...
Abstract PF-04691502 is a potent dual inhibitor of PI3K and mTOR, which are involved in regulating cell growth, proliferation survival. The main objective this work was to develop preclinical pharmacokinetic-pharmacodynamic (PKPD) model for the compound project human efficacious dose. PK mouse obtained following oral dosing described by linear 2-compartment used drive two separate PD models: 1) an exponential growth describing tumor inhibition (TGI) 2) indirect-response changes intratumoral...