A5003836169- Drug Transport and Resistance Mechanisms
- Pharmacogenetics and Drug Metabolism
- Renal Transplantation Outcomes and Treatments
- Lung Cancer Treatments and Mutations
- Lipoproteins and Cardiovascular Health
- Pharmacological Effects and Toxicity Studies
- Biosimilars and Bioanalytical Methods
- Monoclonal and Polyclonal Antibodies Research
- Diabetes Treatment and Management
- Computational Drug Discovery Methods
- Antibiotics Pharmacokinetics and Efficacy
- Cancer therapeutics and mechanisms
- Lung Cancer Research Studies
- Metabolism and Genetic Disorders
- Antiplatelet Therapy and Cardiovascular Diseases
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
- Health Systems, Economic Evaluations, Quality of Life
- Protein purification and stability
- Circadian rhythm and melatonin
- Peptidase Inhibition and Analysis
- Antibiotic Resistance in Bacteria
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Colorectal Cancer Treatments and Studies
- Multiple and Secondary Primary Cancers
Roche (Switzerland)
2019-2025
Jiangsu Hengrui Medicine (China)
2024
Sanofi (France)
2015-2022
Sanofi (United States)
2017
Université de Limoges
2005-2008
Inserm
2007
Centre Hospitalier Universitaire de Limoges
2006
Université de Reims Champagne-Ardenne
2006
Centre Hospitalier Universitaire de Reims
2006
Buprenorphine (BUP) is a synthetic derivative of the morphine alkaloid thebaine. BUP metabolized by <i>N</i>-dealkylation to form active metabolite nor-buprenorphine (Nor-BUP), and both undergo subsequent glucuronidation. Although has been used clinically for years, its metabolism still not fully elucidated. The aim this study was clarify identity human hepatic cytochromes P450 (P450s) involved in investigate other potential metabolites. examined using liver microsomes (HLM) Ad293...
Background The low and highly variable oral bioavailability of the immunosuppressant sirolimus is thought to result partly from genetic polymorphism CYP3A5 gene. Methods This study aimed evaluate contribution single-nucleotide A6986G interindividual variability pharmacokinetics in 47 renal transplant patients at steady state, 21 whom were also followed up for first 3 months after transplantation. administered sirolimus, mycophenolate mofetil, corticosteroids but no calcineurin inhibitor....
Clopidogrel is a prodrug that needs to be converted its active metabolite (clopi-H4) in two sequential cytochrome P450 (P450)-dependent steps. In the present study, dynamic physiologically based pharmacokinetic (PBPK) model was developed Simcyp for clopidogrel and clopi-H4 using specific module four populations with phenotypically different CYP2C19 activity (poor, intermediate, extensive, ultrarapid metabolizers) receiving loading dose of 300 mg followed by maintenance 75 mg. This validated...
Objectives: Rivoceranib (rivo) is a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor. Camrelizumab (cam) humanized monoclonal antibody that specifically binds to programmed cell death receptor 1 (PD-1). The combination (combo) of rivo 250 mg once daily (QD) and cam 200 every 2 weeks (Q2W) has shown favorable clinical efficacy for the treatment patients (pts) with advanced hepatocellular carcinoma (HCC) in pivotal Phase 3 study (Study CARES-310). Hepatotoxicity was one...
ABSTRACT Adult patients with anaplastic lymphoma kinase positive (ALK+) advanced non–small‐cell lung cancer (NSCLC) are treated 600 mg alectinib twice daily (BID) as first‐line treatment. ALK solid and central nervous system (CNS) tumors described in the pediatric population, limited clinical data due to rarity of disease challenges determine right dosing. This study aims inform dose recommendations for by performing a middle‐out physiologically based pharmacokinetic (PBPK) modeling...
Introduction The polymorphic enzyme UGT2B7 metabolizes mycophenolic acid into acyl-mycophenolic acid-glucuronide (AcMPAG), a presumably toxic metabolite. This study aimed at investigating in vitro and vivo the impact on AcMPAG production of: (i) gene G-842A single nucleotide polymorphism, complete linkage disequilibrium with most other known polymorphisms promoter region of this C802T polymorphism exon 2 (UGT2B*2); (ii) immunosuppressants given to renal transplant patients association...
When eye diseases are treated by topical administration, the success of treatment lies in effective drug concentration target tissue. This is why drug's pharmacokinetic, different substructures eye, needs to be explored more accurately during development. The aim present analysis was describe rabbit model, distribution a after ocular instillation selected tissues and fluids.By top-down population approach, we developed validated pharmacokinetics (PopPK) using tissue concentrations (tear,...
Entrectinib is an oral, CNS-active, potent inhibitor of tyrosine receptor kinases A/B/C, kinase ROS proto-oncogene 1, and anaplastic lymphoma approved for use in patients with solid tumors. We describe 3 clinical studies, including one investigating the single/multiple dose pharmacokinetics entrectinib two studies healthy volunteers absorption/distribution/metabolism/excretion (ADME) entrectinib, its relative bioavailability, effect food on pharmacokinetics.The patient study open-label...
Clopidogrel is an antiplatelet agent widely used in cardiovascular diseases and inactive prodrug that needs to be converted active metabolite two sequential metabolic steps. Several CYP450 isoforms involved these steps have been described, although the relative contribution vivo of each enzyme still under debate. CYP2C19 considered major contributor formation. In current study, net formation was determined from exposure clinical studies (one phase I study with well balanced genetic...
Sirolimus is an immunosuppressive drug currently used alone or in combination with cyclosporine. Both drugs undergo extensive metabolism by the CYP 3A enzymes. This study aimed at comparing activity of recombinant (rCYP) 3A4 and 3A5 toward sirolimus, investigating effect cyclosporine on metabolic rate these two cytochromes P450 (P450s), as well impact <i>CYP 3A5*3</i> polymorphism that human liver microsomes (HLMs). Two distinct approaches were used; i.e., measurement (1) hydroxy-sirolimus...
Abstract Glofitamab is a novel T cell bispecific antibody developed for treatment of relapsed‐refractory diffuse large B lymphoma and other non‐Hodgkin's indications. By simultaneously binding human CD20‐expressing tumor cells CD3 on cells, glofitamab induces lysis, in addition to T‐cell activation, proliferation, cytokine release. Here, we describe physiologically‐based pharmacokinetic (PBPK) modeling performed assess the impact glofitamab‐associated transient increases interleukin 6 (IL‐6)...
Adebrelimab, a novel anti-PD-L1 antibody, has been approved by the National Medical Products Administration of China as an intravenous infusion for use in combination with carboplatin and etoposide first-line treatment extensive-stage small-cell lung cancer 2023. A two-compartment model empirical time-varying CL adebrelimab was established based on data from 263 patients receiving body weight-based doses two clinical studies. Significant covariate effects baseline weight, albumin levels,...
Proprotein convertase subtilisin/kexin type 9 inhibition with monoclonal antibodies such as alirocumab significantly reduces low-density lipoprotein-cholesterol levels ± other lipid-lowering therapies. We aimed to develop and qualify a population pharmacokinetics (PopPK) model for in healthy subjects patients, taking into account the mechanistic target-mediated drug disposition (TMDD) process. This TMDD was developed using subset of clinical trial database, including nine phase I/II/III...
Abstract Background Entrectinib is a CNS-active, potent inhibitor of tyrosine receptor kinases A/B/C, ROS1 and anaplastic lymphoma kinase approved for use in patients with solid tumors. We describe the vitro clinical studies investigating potential entrectinib drug-drug interactions. Methods In human biomaterials assessed enzymes involved metabolism, whether modulates activity major cytochrome P450 (CYP) or drug transporter P-glycoprotein. Clinical investigated effect strong CYP3A4...
Abstract Purpose Entrectinib is a central nervous system-active potent inhibitor of tropomyosin receptor kinase (TRK), with anti-tumor activity against neurotrophic NTRK gene fusion-positive tumors. This study investigates the pharmacokinetics entrectinib and its active metabolite (M5) in pediatric patients aims to understand whether dose 300 mg/m 2 once daily (QD) provides an exposure that consistent approved adult (600 mg QD). Methods Forty-three aged from birth 22 years were administered...
Reduction in low-density lipoprotein cholesterol (LDL-C) is associated with decreased risk for cardiovascular disease. Alirocumab, an antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduces LDL-C. Here, we report development of a quantitative systems pharmacology (QSP) model integrating peripheral and liver metabolism, as well PCSK9 function, examine the mechanisms action alirocumab other lipid-lowering therapies, including statins. The predicts changes LDL-C...
Little is known about the chronopharmacokinetics of loratadine, a long‐acting tricyclic antihistamine H1 widely used in treatment allergic diseases. Hence, pharmacokinetics loratadine and its major metabolite, desloratadine, were investigated after 20 mg/kg dose had been orally administered to comparable groups mice (n=33), synchronized for three weeks 12 h light (rest span)/12 dark (activity span). The drug was at different circadian times (1, 9, 17 onset [HALO]). Multiple blood samples...