TAILIEUCHUNG - Does the systemic plasma profile inform the liver profile? Analysis using a physiologically based pharmacokinetic model and individual compounds

The physiologically based pharmacokinetic (PBPK) model for liver transporter substrates has been established previously and used for predicting drug–drug interactions (DDI) and for clinical practice guidance. So far, nearly all the published PBPK models for liver transporter substrates have one or more hepatic clearance processes (., active uptake, passive diffusion, metabolism, and biliary excretion) estimated by fitting observed systemic data. The estimated hepatic clearance processes are then used to predict liver concentrations and DDI involving either systemic or liver concentration. However, the accuracy and precision of such predictions are unclear. In this study, we try to address this question by using the PBPK model to generate simulated compounds for which we know both systemic and liver profiles. We then developed an approach to assess the accuracy and precision of predicted liver concentration. With hepatic clearance processes estimated using plasma data, model predictions of liver are typically accurate (., true value is bounded by predicted maximum and minimum); however, only for a few compounds are predictions also precise. | Does the systemic plasma profile inform the liver profile Analysis using a physiologically based pharmacokinetic model and individual compounds

• Y khoa - Dược
• Identifiability analysis
• Liver transporter
• Physiologically based pharmacokinetic model
• Systemic plasma profile
• Liver profile
• báo cáo khoa học
• báo cáo hóa học
• công trình nghiên cứu về hóa học
• tài liệu về hóa học
• cách trình bày báo cáo
• BMC Bioinformatics
• Constrained parameter estimation
• Kalman filter
• Kinetic models
• Parameter estimation framework
• Bacteriological profile
• Ascitic fluid
• Chronic liver disease
• Antibiotic susceptibility
• Ascitic fluid among patients diagnosed
• BMC Cancer
• C3H mice
• DNA methylation
• Liver tumors
• Reduced representation bisulfite sequencing
• Fruit juice extract
• Azadirachta indica
• Liver enzymes
• Plasmodium berghei
• Lipid profile