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2 edition of Physiologically-based pharmacokinetic modelling of L-asparaginase. found in the catalog.

Physiologically-based pharmacokinetic modelling of L-asparaginase.

Krista Lyn Traynor

Physiologically-based pharmacokinetic modelling of L-asparaginase.

by Krista Lyn Traynor

  • 167 Want to read
  • 14 Currently reading

Published .
Written in English


About the Edition

L-asparaginase (ASNase) is a standard agent in the treatment of acute lymphocytic leukemia, but its mechanism of elimination has not yet been determined. Possible methods include hepatic and renal clearance, although renal clearance has been deemed unlikely. A physiologically-based pharmacokinetic model, including plasma, liver, kidney, muscle and gastrointestinal tract compartments, was constructed for ASNase to study the factors that affect its elimination, and to determine if renal clearance can be ruled out. Simulations were performed for hepatic and renal clearances alone and hepatic and renal clearances together. The model was fit to animal data to estimate the tissue-to-plasma partition coefficients and clearance rates. The optimal partition coefficients were 0.01-0.077 for the liver, kidneys and gastrointestinal tract, and 0.001-0.0077 for the muscles. Based on the model, the following methods of ASNase elimination are possible: (1) hepatic only, (2) hepatic and renal, (3) renal only and (4) other methods not considered here.

The Physical Object
Pagination123 leaves.
Number of Pages123
ID Numbers
Open LibraryOL19216378M
ISBN 100494071478

  Physiologically based pharmacokinetic (PBPK) models differ from classical PK models in that they include specific compartments for tissues involved in exposure, toxicity, biotransformation and clearance processes connected by blood flow (Figure 1).Compartments and blood flows are described using physiologically meaningful parameters, which allows for interspecies . "Variability of physiologically based pharmacokinetic (PBPK) model parameters and their effect on PBPK model predictions in a risk assessment for perchloroethylene (PCE)." Toxicol. Toxicol. Let. .

Physiologically based pharmacokinetic (PBPK) modeling and simulation in drug discovery and development Abdul Naveed Shaik & Ansar Ali Khan ADMET & DMPK 7(1) () ; DOI: /admet   Physiologically-based pharmacokinetic modeling for first-in-human predictions: an updated model building strategy illustrated with challenging industry case studies. Clin. Pharmacokinet. 58(6), – ().Crossref, Medline, CAS, Google Scholar; 5. Korzekwa K, Nagar S.

The idea of body compartments has its origins in physiology and antedates their use in both physiologically-based predictive pharmacokinetic models and in the simpler compartmental models . Physiologically Based Pharmacokinetic Modeling AP Spring -- An online course for both on-campus and distance students through K-State Global campus. Learn online. Develop professionally. Connect globally. Course Overview This course is designed to teach physiologically based pharmacokinetic (PBPK) modeling at a very basic level.


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Physiologically-based pharmacokinetic modelling of L-asparaginase by Krista Lyn Traynor Download PDF EPUB FB2

Abstract. Physiologically based pharmacokinetic (PBPK) modeling is a computational process that simulates the absorption, distribution, metabolism, and excretion of a substance in the body of an organism based on the interrelationships among key physiological, biochemical, and physicochemical factors using mathematical equations.

Physiologically-based pharmacokinetic (PBPK) modeling is becoming increasingly important in human health risk assessments and in supporting pharmacodynamic modeling for toxic responses.

Organized by classes of compounds and modeling purposes so users can quickly access information, this is the first comprehensive reference of its by: Purchase Physiologically Based Pharmacokinetic (PBPK) Modeling - 1st Edition. Print Book & E-Book. ISBNThe only book dedicated to physiologically-based pharmacokinetic modeling in pharmaceutical science.

Physiologically-based pharmacokinetic (PBPK) modeling has become increasingly widespread within the pharmaceutical industry over the last decade, but without one dedicated book that provides the information researchers need to learn these new techniques, its applications are severely. A definitive, single source of information on PBPK modeling Physiologically-based pharmacokinetic (PBPK) modeling is becoming increasingly important in human health risk assessments and in supporting pharmacodynamic modeling for toxic responses.

Organized by classes of compounds and modeling purposes so users can quickly access information, this is the first comprehensive reference. Semi-physiologically based drug-metabolite model of dextromethorphan and dextrorphan.

D stands for dextromethorphan and M for dextrorphan; G is the gut; S is the systemic circulation; P is a peripheral space; F is the bioavailability; k a is the absorption rate constant; CL and CL M are the clearances of the drug and metabolite, respectively; V and V M are the volumes of distribution of the.

Buprenorphine plays a crucial role in the therapeutic management of pain in adults, adolescents and pediatric subpopulations. However, only few pharmacokinetic studies of buprenorphine in children, particularly neonates, are available as conducting clinical trials in this population is especially challenging.

Physiologically-based pharmacokinetic (PBPK) modeling allows the prediction of drug. The toxicity of arsenic (As) targets specific tissues of organisms, while the biotransportation of As among the tissues of fish remains poorly understood.

In the present study, radiotracer techniques followed by a physiologically based pharmacokinetic (PBPK) modeling were applied to simulate the biotransportation (absorption, distribution, and elimination) of 73As(V) and biotransformation of.

Physiologically Based Pharmacokinetic Analyses — Format and practices for the conduct of PBPK modeling and simulation or the appropriateness of PBPK analyses for a particular drug or a drug. In this regard, physiologically based pharmacokinetic (PBPK) modeling is 1 quantitative support tool for assessing nanoparticle hazards recommended by the Organization for Economic Cooperation and Development and the new European Union regulatory framework, Registration, Evaluation, and Authorization of Chemicals.

15 This tool has been well. INTRODUCTION. Physiologically based pharmacokinetic (PBPK) models can deliver valuable information during various stages of drug development and research (1–4).Their ability to incorporate information about maturation, growth, and age dependency of anatomical and physiological processes facilitates their use to extrapolate drug pharmacokinetics from adults to children and to.

Sager JE, et al. Physiologically based pharmacokinetic (PBPK) modeling and simulation approaches: a systematic review of published models, applications, and model verification.

Drug Metab Dispos. ;43(11)– A physiologically-based pharmacokinetic (PBPK) model is a computational tool used to predict concentration-time profiles of a compound in various tissues, and to extrapolate pharmacokinetics of.

Schematic of the physiologically‐based pharmacokinetic (PBPK) model: (a) full PBPK model, (b) organ‐level model, (c) endosomal‐levelneonatal Fc receptor; Ab, antibody; FR, volume fraction of pinocytosis from vascular space (apical); CLup, pinocytotic uptake rate of endothelial cells; 1‐FR, volume fraction of pinocytosis from intestitial space (basolateral); kdeg_FcRn_Ab.

A physiologically-based pharmacokinetic (PBPK) model was developed to describe the biodistribution data in mice. To assess the potential for interspecies extrapolation, organism-specific parameters in the model were adapted to represent rats, and the rat PBPK model was subsequently evaluated with PK data for citrate-capped AuNPs from literature.

The Food and Drug Administration (FDA) will convene a workshop on model informed drug development approaches using physiologically based pharmacokinetic analyses as part of this workshop series. The only book dedicated to physiologically-based pharmacokinetic modeling in pharmaceutical science Physiologically-based pharmacokinetic (PBPK) modeling has become increasingly widespread within the pharmaceutical industry over the last decade, but without one dedicated book that provides the information researchers need to learn these new techniques, its applications are seve.

Two-pore physiologically based pharmacokinetic model with de novo derived parameters for predicting plasma PK of different size protein therapeutics Zhe Li, Dhaval K. Shah Pages Continue reading. Title:Physiologically Based Pharmacokinetic Models: Integration of In Silico Approaches with Micro Cell Culture Analogues VOLUME: 13 ISSUE: 6 Author(s):A.

Chen, M. Yarmush and T. Maguire Affiliation:Rutgers University, Department of Biomedical Engineering, Taylor Road, Piscataway NJ Keywords:Physiological based pharmacokinetic models, microfluidic, cell culture analogue. Physiologically based pharmacokinetic (PBPK) models are increasingly used by drug developers to evaluate the effect of patient factors on drug exposure.

Between June and Decemberthe Office of Clinical Pharmacology at the US Food and Drug Administration (FDA) received 25 submissions containing PBPK analyses.

Physiologically based pharmacokinetic (PBPK) modeling is a mathematical modeling technique for predicting the absorption, distribution, metabolism and excretion (ADME) of synthetic or natural chemical substances in humans and other animal species.

PBPK modeling is used in pharmaceutical research and drug development, and in health risk assessment for cosmetics or general chemicals.A Physiologically Based Pharmacokinetic Model of Voriconazole Integrating Time-Dependent Inhibition of CYP3A4, Genetic Polymorphisms of CYP2C19 and Predictions of Drug-Drug Interactions.

Author: Li X, Frechen S, Moj D, Lehr T, Taubert M, Hsin CH. 14 PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODELING OF POPULATIONS Introduction Population Modeling with PBPK Healthy to Target Patient Population: Impact of Disease on Pharmacokinetics Modeling Subpopulations: Impact of Age, Gender, Co-morbidities, and Genetics on Pharmacokinetics