A5090225500- Polyomavirus and related diseases
- Bacteriophages and microbial interactions
- Diabetes Treatment and Management
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Plant Virus Research Studies
- Pharmacology and Obesity Treatment
- Drug Transport and Resistance Mechanisms
- Inhalation and Respiratory Drug Delivery
- Acute Lymphoblastic Leukemia research
- Pharmacological Effects and Toxicity Studies
- Pregnancy and Medication Impact
- Neuroendocrine Tumor Research Advances
- Cancer Immunotherapy and Biomarkers
- Neuropeptides and Animal Physiology
- Monoclonal and Polyclonal Antibodies Research
- Asthma and respiratory diseases
- Ovarian cancer diagnosis and treatment
- Neuroblastoma Research and Treatments
- Respiratory viral infections research
- Pneumocystis jirovecii pneumonia detection and treatment
- Pharmaceutical studies and practices
- Advanced Drug Delivery Systems
- Cardiac Ischemia and Reperfusion
- Renal cell carcinoma treatment
Ono Pharmaceutical (United States)
2019-2024
Shaoyang University
2024
Research & Development Institute
2022
Merck (Germany)
2020
Pfizer (United States)
2010-2013
University of Minnesota
2005
University of Nebraska Medical Center
2003
Nebraska Medical Center
2003
University of Tsukuba
1996
Avelumab, a human anti–programmed death ligand 1 immunoglobulin G1 antibody, has shown efficacy and manageable safety in multiple tumors. A two‐compartment population pharmacokinetic model for avelumab incorporating intrinsic extrinsic covariates time‐varying clearance ( CL ) was identified based on data from 1,827 patients across three clinical studies. Of 14 tumor types, decrease over time more notable metastatic Merkel cell carcinoma squamous of the head neck, which had maximum decreases...
Avelumab, an anti–programmed death‐ligand 1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma and platinum‐treated urothelial carcinoma, was initially with a 10 mg/kg weight‐based dose. We report pharmacokinetic (PK)/pharmacodynamic analyses avelumab comparing dosing flat 800 mg dose, developed using data from 1,827 patients enrolled in 3 clinical trials (NCT01772004, NCT01943461, NCT02155647). PK metrics were simulated flat‐dosing regimens summarized by...
Avelumab (anti-PD-L1) is an approved anticancer treatment for several indications. The JAVELIN Gastric 100 phase III trial did not meet its primary objective of demonstrating superior overall survival (OS) with avelumab maintenance versus continued chemotherapy in patients advanced gastric cancer/gastroesophageal junction cancer; however, the OS rate was numerically higher at timepoints after 12 months. Machine learning (random forests, SIDEScreen, and variable-importance assessments) used...
Pemetrexed disodium is a novel antifolate that exhibits potent inhibitory effects on multiple enzymes in folate metabolism. Phase II/III clinical trials have shown pemetrexed effective against various solid tumors. Like methotrexate, may be useful treatment of primary and secondary brain In this study, we examined the central nervous system (CNS) distribution interaction with an organic anion transport inhibitor indomethacin. Male Wistar rats were administered by either single intravenous...
The disposition of 3,3-difluoropyrrolidin-1-yl{(2<i>S</i>,4<i>S</i>)-4-[4-(pyrimidin-2-yl)piperazin-1-yl]pyrrolidin-2-yl}methanone (PF-00734200), a dipeptidyl peptidase IV inhibitor that progressed to phase 3 for the treatment type 2 diabetes, was examined in rats, dogs, and humans after oral administration single dose [<sup>14</sup>C]PF-00734200. Mean recoveries administered radioactivity were 97.1, 92.2, 87.2% humans, respectively. majority radioactive detected urine dogs feces rats....
Abstract Like other monoclonal antibodies, immune checkpoint inhibitors may be immunogenic in some patients, potentially affecting pharmacokinetics (PKs) and clinical outcomes. In post hoc analyses, we characterized antidrug antibody (ADA) development with avelumab monotherapy patients metastatic Merkel cell carcinoma (mMCC) from the JAVELIN 200 trial (first‐line [1L; N = 116] second‐line or later [≥2L; 88] cohorts) advanced urothelial (aUC) Bladder 100 (1L maintenance [ 350]) Solid Tumor...
Abstract Avelumab is an anti–PD‐L1 monoclonal antibody approved as monotherapy for Merkel cell carcinoma (MCC) and urothelial (UC), in combination with axitinib advanced renal (aRCC). Although initially weight‐based dosing (10 mg/kg intravenously [IV] every 2 weeks [Q2W]), avelumab was subsequently flat (800 mg IV Q2W) based on population pharmacokinetic (PopPK), exposure‐efficacy, exposure‐safety modeling MCC UC. Here, through simulation, we provide justification a flat‐dose regimen of plus...
Glucocorticoids are widely used in inhalation aerosol therapy for wheezing diseases. This study aims to explore guardians' knowledge and attitude towards inhaled corticosteroids (ICS) the medication compliance of children with diseases China.
PF-734200 is a potent and selective oral dipeptidyl peptidase-4 (DPP-4) inhibitor. This study assessed the efficacy safety of at dose rates 20 30 mg/day in subjects with Type 2 diabetes mellitus inadequately controlled on metformin monotherapy. was placebo-controlled, double-blind, randomized, multicentre, 12 week study. Subjects were eligible if screening glycosylated haemoglobin (HbA(1c) ) 7-11% (53.0-96.7 mmol/mol) they had been receiving monotherapy for ≥2 months. an insulin secretagogue...
The purpose of this phase 2, multicentre, randomized, double-blind, placebo-controlled, 12-week dose-ranging study was to assess the efficacy, safety, and tolerability dipeptidyl peptidase-IV (DPP-IV) inhibitor PF-734200 in adult subjects with type 2 diabetes who were on a stable dose metformin. Men women inadequate glycaemic control metformin as their sole medication randomized placebo or mg, 5 10 20 mg every day. A population subset underwent mixed meal tolerance tests (MMTT) at baseline...
Cellular barriers in the central nervous system (CNS) present a formidable challenge delivery of drugs to brain. These include blood-brain barrier (BBB) and blood-cerebrospinal fluid (BCSFB). Of these, given surface area diffusional distance considerations, BBB may be more important drug transport bulk brain parenchyma. With development increasing numbers new compounds treat CNS diseases, quantitative methods examine are necessary. Several past have been used, e.g., whole homogenates,...
A phase I/II trial evaluated the safety, antitumor activity, and pharmacokinetics of avelumab (anti-PD-L1 antibody) in pediatric patients with refractory/relapsed solid tumors (NCT03451825). This study aimed to inform dose selection populations using population pharmacokinetic modeling simulations. Patients aged < 18 years enrolled I received 10 or 20 mg/kg intravenously every 2 weeks. model was developed via frequentist prior approach. Pharmacokinetic parameters from 21 who (n = 6) 15) were...
To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of PF-00734200, a potent dipeptidyl peptidase-IV (DPP-IV) inhibitor, in Japanese subjects, compare results with those Western subjects.Eight healthy subjects received single dose PF-00734200 10 mg, 100 or placebo. Another 8 20 mg placebo once daily for 6 days. Serum urine PK, plasma DPP-IV activity, glucagon-like peptide 1 (GLP-1) levels were measured.Linear pharmacokinetics was observed over range - mg. Following...
Abstract Purpose: Empirical time-varying clearance models have been reported for several immune checkpoint inhibitors, including avelumab (anti–programmed death ligand 1). To investigate the exposure-response relationship avelumab, we explored semimechanistic pharmacokinetic (PK)–tumor growth dynamics (TGD) models. Patients and Methods: Plasma PK data were pooled from three phase I II trials (JAVELIN Merkel 200, JAVELIN Solid Tumor, Tumor JPN); tumor size (TS) collected patients with...
Increased glucose flux through the polyol pathway and resultant oxidative stress is thought to be a major mechanistic contributor microvascular diabetic complications. Inhibition of this can blocked inhibition either 2 enzymes, aldose reductase (AR) or sorbitol dehydrogenase (SDH). This report describes pharmacokinetics, biomarker pharmacodynamics, safety CP-642,931, potent specific inhibitor (SDI). CP-642,931 was administered for 7 days 57 healthy volunteers in doses ranging from 1 35 mg...