Tag: Simcyp
Physiologically-based Pharmacokinetic Model for Topotecan in Mice
Topotecan is a chemotherapeutic agent of choice for the second-line treatment of recurrent ovarian cancer. In this article, we have developed a physiologically based pharmacokinetic model to characterize and predict topotecan concentrations in mouse plasma and tissues. Single intravenous (IV) doses (5, 10 and 30 mg/kg) of topotecan were administered to male Swiss Webster mice, … Continued
Physiologically-based Pharmacokinetics in Drug Development and Regulatory Science
The application of physiologically-based pharmacokinetic (PBPK) modeling is coming of age in drug development and regulation, reflecting significant advances over the past 10 years in the predictability of key pharmacokinetic (PK) parameters from human in vitro data and in the availability of dedicated software platforms and associated databases. Specific advances and contemporary challenges with respect … Continued
PBPK Modeling of Inter-individual Variability in the Pharmacokinetics of Environmental Chemicals
Generic PBPK models, applicable to a large number of substances, coupled to parameter databases and QSAR modules, are now available for predictive modelling of inter-individual variability in the absorption, distribution, metabolism and excretion of environmental chemicals. When needed, Markov chain Monte Carlo methods and multilevel population models can be jointly used for a Bayesian calibration … Continued
Simulation of Virtual Human Subjects to Investigate the Impact of CYP2C19*17/*17 on Omeprazole Exposure
Prediction of Human Intestinal Metabolism of CYP3A Substrates Using the Advanced, Dissolution, Absorption and Metabolism (ADAM) Model
Physiologically-based Mechanistic Modeling to Predict Complex Drug–drug Interactions Involving Simultaneous Competitive and Time-dependent Enzyme Inhibition by Parent Compound and Its Metabolite in Both Liver and Gut—The Effect of Diltiazem on the Time-course of Exposure to Triazolam
The aim of this study was to predict the magnitude of metabolic drug-drug interaction (mDDI) between triazolam and diltiazem and its primary metabolite N-desmethyldiltiazem (MA).Relevant in vitro metabolic and inhibitory data were incorporated into a mechanistic physiologically based pharmacokinetic model within Simcyp (Version 9.1) to simulate the time-course of changes in active CYP3A4 content in … Continued
Physiologically-based Pharmacokinetics (PBPK)
Allometric scaling is widely used to predict human pharmacokinetic parameters from preclinical species, and many different approaches have been proposed over the years to improve its predictive performance. Nevertheless, prediction errors are commonly observed in the practical application of simple allometry, for example, in cases where the hepatic metabolic clearance is mainly determined by enzyme … Continued
Pharmacokinetic Predictions in Children by Using the Physiologically-based Pharmacokinetic Modeling
Nowadays, 50-90% of drugs used in children have never been actually studied in this population. Consequently, either our children are often exposed to the risk of adverse drug events or to lack of efficacy, or they are unable to benefit from a number of therapeutic advances offered to adults, as no clinical study has been properly performed in children. Actually … Continued
The Effects of CYP3A4 Inhibition on Erlotinib Pharmacokinetics: Computer-based Simulation (Simcyp) Predicts In Vivo Metabolic Inhibition
BACKGROUND: Erlotinib is an orally active antitumor agent. Analyses in vitro using human liver microsomes and recombinant enzymes showed thaterlotinib was metabolized primarily by CYP3A4, with a secondary contribution from CYP1A2. METHODS: A computer-based simulation model, SimCYP®, predicted that CYP3A4 contributed to approximately 70% of the metabolic elimination oferlotinib, with CYP1A2 being responsible for the other approximately 30%. A drug-drug interaction study was therefore conducted for erlotinib and … Continued
