TAILIEUCHUNG - Development of a physiologically based pharmacokinetic model to predict disease-mediated therapeutic protein–drug interactions: Modulation of multiple cytochrome P450 enzymes by Interleukin-6

Disease-mediated therapeutic protein–drug interactions have recently gained attention from regulatory agencies and pharmaceutical industries in the development of new biological products. In this study, we developed a physiologically based pharmacokinetic (PBPK) model using SimCYP to predict the impact of elevated interleukin-6 (IL-6) levels on cytochrome P450 (CYP) enzymes and the treatment effect of an anti-IL-6 monoclonal antibody, sirukumab, in patients with rheumatoid arthritis (RA). A virtual RA patient population was first constructed by incorporating the impact of systemic IL-6 level on hepatic and intestinal expression of multiple CYP enzymes with information from in vitro studies. Then, a PBPK model for CYP enzyme substrates was developed for healthy adult subjects. After incorporating the virtual RA patient population, the PBPK model was applied to quantitatively predict pharmacokinetics of multiple CYP substrates in RA patients before and after sirukumab treatment from a clinical cocktail drug interaction study. | Development of a physiologically based pharmacokinetic model to predict disease-mediated therapeutic protein drug interactions Modulation of multiple cytochrome P450 enzymes by Interleukin-6

• Y khoa - Dược
• Cytochrome P450
• Interleukin 6
• Monoclonal antibody
• Therapeutic protein–drug interaction
• Multiple cytochrome P450 enzymes
• Nghiên cứu Cytochrome P450
• Đặc điểm cấu tạo Cytochrome P450
• Cơ chế phản ứng Cytochrome P450
• Hệ thống oxygenase ở mô động vật
• Cytochrome P450 ở vi sinh vật
• Nghiên cứu ứng dụng cytochrome P450
• Scientific reports
• breast cancer
• medicine
• monooxygenases
• metabolism
• Camellia sinensis L
• Kuntze
• Cytochrome P450 monooxygenase
• Molecular and in silico cloning
• Seasonal gene expression
• Nicotinamide adenine
• Binh Chau hot spring
• Thermostable enzyme
• HiSeq Illumina
• Bulk chemicals
• Food ingredient
• Luận văn Thạc sĩ
• Công nghệ thông tin
• Công nghệ nano sinh học
• Gen mã hóa cytochrome P450
• Suối nước nóng Bình Châu
• BMC Pharmacology and Toxicology
• Antimalarial drug
• Metabolic drug interaction
• Plumbaginaceae family
• Aldosterone synthase gene
• Cytochrome P450 11B2
• Mineralocorticoid receptors
• Single nucleotide polymorphism
• Coronary artery disease
• Taiwan women
• BMC Plant Biology
• Gramineae crops
• Expression regulation
• Growth and development
• Drought stress
• BMC Cancer
• Soluble epoxide hydrolase
• Epoxyeicosatrienoic acids
• Several cancer diseases
• BMC Genomics
• Intron map
• Genome wide promoter analysis
• Tissue specific promoter
• Gene duplication
• Expression profile
• Journal of Chemistry
• PEGylated quinoline
• Colon cancer
• P glycoprotein
• Cytochrome P450 enzyme
• Polyethylene glycol (PEG)
• Polymeric carriers conjugated
• NADPH cytochrome P450 reductase
• Lake Van fish
• Hydrophobic α helix transmembrane
• Methionine synthase reductase
• Chronic myeloid leukemia
• Drug metabolizing enzymes
• Glutathione S transferases
• Tyrosine kinase inhibitors
• fatty acids
• physiological roles
• Buccal cells
• Occupational exposure
• Restriction fragment length polymorphism
• Cytochrome P450 1A1
• Report medicine
• traditional medicine
• gastric cancer
• hormone medicine
• tumor cells
• Structural biochemistry
• oxidation
• bacteria
• CYP structure interface
• Template based modelling
• Metabolic pathways
• Three dimensional
• BMC Veterinary Research
• Metabolic ratio
• Cytochrome 2D6
• CYP2D6 gene
• báo cáo khoa học
• báo cáo y học
• công trình nghiên cứu về y học
• tài liệu về y học
• cách trình bày báo cáo
• medical knowledge
• medical research
• analysis of cytoplasmic