Dataset Information

Sier2017_E2_combined

ABSTRACT: Using scaling from PhysB model Blood flow in L/hr Compartments in Kg Baseline as ~0.003nM Free E2 in Blood_venous E2 biosynthesis rate constant = 2 E2 biosynthesis species = 1nM CLeh = 5 CLint = metabolic model T:P = 0.286

SUBMITTER: Nick J. Plant

PROVIDER: MODEL1711210002 | BioModels | 2018-02-02

REPOSITORIES: BioModels

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Publications

Linking physiologically-based pharmacokinetic and genome-scale metabolic networks to understand estradiol biology.

Sier Joanna H JH Thumser Alfred E AE Plant Nick J NJ

BMC systems biology 20171215 1

<h4>Background</h4>Estrogen is a vital hormone that regulates many biological functions within the body. These include roles in the development of the secondary sexual organs in both sexes, plus uterine angiogenesis and proliferation during the menstrual cycle and pregnancy in women. The varied biological roles of estrogens in human health also make them a therapeutic target for contraception, mitigation of the adverse effects of the menopause, and treatment of estrogen-responsive tumours. In ad ...[more]

PMID: 29246152

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Project description:Basic PBPK (Physiologically Based PharmacoKinetic) model of Acetaminophen. This is a basic model of Acetaminophen (APAP, Paracetamol) pharmacokinetics in humans. Many of the model parameters (compartment volumes, volumetric flow rates, etc.) are scaled allometrically based on the body weight (BW) raised to the 3/4 power. Because of that, the assigned values of many of the parameters are recalculated at run time and are different than the default values for the particular entity (e.g., the volume of a compartment and the volumetric flow rate between compartments). APAP dose is initially given in grams (APAP_Dose_gram), which is converted to moles via the APAP molecular weight (APAP_MW). APAP quantities throughout the rest of the models are given in moles. The base parameters are for a 70Kg human and a pharmacological oral dose of 1.4 gram of APAP. Metabolism is modelled as a single ODE in the liver compartment and the metabolite does not leave that compartment. This model is loosely based on the model of Wambaugh and Shaw (PLoS Comput Biol. 2010 Apr 22;6(4):e1000756. doi: 10.1371/journal.pcbi.1000756. Pubmed ID: PMID- 20421935) with the following changes: The lung lumen compartment was omitted. A kidney compartment was added. Glomerular Filtration is from the kidney compartment. The APAP dose was changed to 1.4g. The gut adsorption rate constant (KGutabs), tissue partition coefficients and liver metabolism rate constant (CLmetabolism) were fit using the human in vivo data of Critchley (Critchley, J. A., Critchley, L. A. H., Anderson, P. J., and Tomlinson, B. 2005 Journal of clinical pharmacy and therapeutics, 30(2), 179-184). To model the extensive re-adsorption of APAP from the kidney tubules back into the blood the QGfr value is modified. This was done by changing the scaling parameter QGFR_ref value from 0.31 to 0.039, resulting in a decrease in the QGfr value of 8 fold (from 7.2 L/hr to 0.91 L/hr). The parameters in this file are the REFSIM parameters from our publication.

Dataset Information

Sier2017_E2_combined

Publications

Linking physiologically-based pharmacokinetic and genome-scale metabolic networks to understand estradiol biology.

Similar Datasets

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