23032015175934459m0500
type: Ontology
sem sim version: 0.2
has cell m ldocumentation: <documentation xmlns="http://cellml.org/tmp-documentation"> <articleinfo> An Age-Dependent Physiologically Based Pharmokinetic Model of Methadone Distribution and Metabolism <author> <firstname>Catherine</firstname> <surname>Lloyd</surname> <affiliation> <shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil> </affiliation> </author> </articleinfo> Model Status This CellML version of the model has been checked in COR and PCEnv. It will recreate published results, although it only models a single organ (the liver) as well as the veins and arteries, and is based on a 5 year old boy. The model cannot replicate the population analysis described in the paper, which needs stochastic tools that are unavailable to CellML at present. <sect1 id="sec_structure"> Model Structure Abstract: Limited pharmacokinetic (PK) and pharmacodynamic (PD) data are available to use in methadone dosing recommendations in pediatric patients for either opioid abstinence or analgesia. Considering the extreme inter-individual variability of absorption and metabolism of methadone, population-based PK would be useful to provide insight into the relationship between dose, blood concentrations, and clinical effects of methadone. To address this need, an age-dependent physiologically based pharmacokinetic (PBPK) model has been constructed to systematically study methadone metabolism and PK. The model will facilitate the design of cost-effective studies that will evaluate methadone PK and PD relationships, and may be useful to guide methadone dosing in children. The PBPK model, which includes whole-body multi-organ distribution, plasma protein binding, metabolism, and clearance, is parameterized based on a database of pediatric PK parameters and data collected from clinical experiments. The model is further tailored and verified based on PK data from individual adults, then scaled appropriately to apply to children aged 0-24 months. Based on measured variability in CYP3A e…
has cell m lrdf markup: <rdf:RDF xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:j.0="http://imc.org/vCard/3.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/"> <rdf:Description rdf:about="http://www.cellml.org/cellml/1.0"> <cmeta:modification> <rdf:Description rdf:about="rdf:#a05351ef-cabb-4a19-9059-f86709913fa0"> <cmeta:modifier> <rdf:Description rdf:about="rdf:#77025e1f-f75b-4f8f-a634-8729cfd40944"> <vCard:N> <rdf:Description rdf:about="rdf:#23c26476-20ca-4720-a98b-acc3a33f679e"> <vCard:Other>May</vCard:Other> <vCard:Family>Lloyd</vCard:Family> <vCard:Given>Catherine</vCard:Given> </rdf:Description> </vCard:N> </rdf:Description> </cmeta:modifier> <rdf:value>Fixed the units and one of the equations</rdf:value> <dcterms:modified> <rdf:Description rdf:about="rdf:#ec62f86a-22c5-4ade-ba5d-592578170df9"> <dcterms:W3CDTF>2007-09-06T14:38:34+12:00</dcterms:W3CDTF> </rdf:Description> </dcterms:modified> </rdf:Description> </cmeta:modification> <cmeta:modification> <rdf:Description rdf:about="rdf:#2b8a6e1d-014d-4564-a3f2-25536c50bc63"> <cmeta:modifier> <rdf:Description rdf:about="rdf:#79bbc0d1-909d-4350-8459-47d57d417e74"> <vCard:N> <rdf:Description rdf:about="rdf:#f8684c5a-b134-4bc1-82b7-23ec9c63fcf4"> <vCard:Family>Nunns</vCard:Family> <vCard:Given>Geoffrey</vCard:Given> </rdf:Description> </vCard:N> </rdf:Description> </cmeta:modifier> <rdf:value>Redirected some variable mapping to recreate published results, also had to input new values for volume of blood.</rdf:value> <dcterms:modified> <rdf:Description rdf:about="rdf:#32ccad66-7490-4d45-86b7-37ca2ec544d5"> <dcterms:W3CDTF>2008-06-04T14:58:39+12:00</dcterms:W3CDTF> </rdf:Description> </dcterms:modified> </rdf:Description> </cmeta:modification> <dc:creator> <rdf:Description rdf:about="rdf:#7c18fe8f-03b6-4853-9abb-553209df1377"> <vCard:N> <rdf:Descr…
model description: Age-Dependent Physiologically Based Pharmacokinetic Model of Methadone Distribution and Metabolism
legacy code URI: C:\Users\thomp_000\Dropbox\Work Related\Annotated Models\Yang_2006\yang_tong_mccarver_hines_beard_2006.cellml
modeler name: Chris Thompson
annotator name: Chris Thompson
cellml URL: https://models.physiomeproject.org/exposure/95df296549513e45bca595a9b6011446/yang_tong_mccarver_hines_beard_2006.cellml/view
model name: yang_tong_mccarver_hines_beard_2006_version01
model id: yang_tong_mccarver_hines_beard_2006_version01

Total volume of shape
type: Class
subclass of: Reference physical property
subclass of: Restriction
  on property: refersTo
  has value: Total volume of shape

Fluid volume
type: Class
subclass of: Reference physical property
subclass of: Restriction
  on property: refersTo
  has value: Fluid volume

Chemical concentration
type: Class
subclass of: Reference physical property
subclass of: Restriction
  on property: refersTo
  has value: Chemical concentration

Chemical concentration flow rate
type: Class
subclass of: Reference physical property
subclass of: Restriction
  on property: refersTo
  has value: Chemical concentration flow rate

methadone
type: Class
subclass of: Reference physical entity
subclass of: Restriction
  on property: refersTo
  has value: methadone

2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
type: Class
subclass of: Reference physical entity
subclass of: Restriction
  on property: refersTo
  has value: 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine

2-Ethyl-5-methyl-3,3-diphenyl-1-pyrroline
type: Class
subclass of: Reference physical entity
subclass of: Restriction
  on property: refersTo
  has value: 2-Ethyl-5-methyl-3,3-diphenyl-1-pyrroline

Portion of plasma
type: Class
subclass of: Reference physical entity
subclass of: Restriction
  on property: refersTo
  has value: Portion of plasma

Organ
type: Class
subclass of: Reference physical entity
subclass of: Restriction
  on property: refersTo
  has value: Organ

Portion of arterial blood
type: Class
subclass of: Reference physical entity
subclass of: Restriction
  on property: refersTo
  has value: Portion of arterial blood

Portion of venous blood
type: Class
subclass of: Reference physical entity
subclass of: Restriction
  on property: refersTo
  has value: Portion of venous blood

Portion of blood
type: Class
subclass of: Reference physical entity
subclass of: Restriction
  on property: refersTo
  has value: Portion of blood

Composite physical entity
type: Class
subclass of: Physical entity
disjoint with: Custom physical entity
disjoint with: Reference physical entity
comment: A physical entity that is defined by linking multiple physical entity terms with structural relations.

Computation
type: Class
subclass of: Computational model component
disjoint with: Data structure
comment: A mathematical and/or logical expression that determines the value of a data structure.

Computational model component
type: Class
subclass of: SemSim component
disjoint with: Physical model component
comment: An element of a SemSim model that relates to the mathematical or logical representation of physical quantities or qualities.

Custom physical dependency
type: Class
subclass of: Physical dependency
disjoint with: Reference physical dependency
comment: A physical dependency defined in a specific SemSim model.

Custom physical entity
type: Class
subclass of: Physical entity
comment: A physical entity defined in a specific SemSim model.

Custom physical process
type: Class
subclass of: Physical process
comment: A physical process defined in a specific SemSim model.

Custom physical property
type: Class
subclass of: Physical property
disjoint with: Reference physical property
comment: A physical property defined in a specific SemSim model.

Data structure
type: Class
subclass of: Computational model component
comment: A computational element that stores numerical and/or logical information related to the model.

Decimal
type: Class
subclass of: Real
disjoint with: Integer
comment: A data structure whose value is limited to decimals.

Integer
type: Class
subclass of: Real
comment: A data structure whose value is limited to the whole numbers.

MMLchoice
type: Class
subclass of: Real
comment: A data structure unique to JSim's Mathematical Modeling Language (MML) used to set one or more model input values at runtime.

Physical dependency
type: Class
subclass of: Physical model component
disjoint with: Physical entity
disjoint with: Physical process
disjoint with: Physical property
comment: A quantitative relation between values of physical properties that occurs over a span of time and that determines the time-course of a physical process.

Physical entity
type: Class
subclass of: Physical model component
disjoint with: Physical process
disjoint with: Physical property
comment: A physics analytical entity that represents the material, energy, and/or information content of material or immaterial, space-occupying continuants.

Physical model component
type: Class
subclass of: SemSim component
comment: A SemSim model element used to represent, in whole or in part, the physical meaning of a computational element.

Physical process
type: Class
subclass of: Physical model component
disjoint with: Physical property
comment: A physical processural entity that is a flow, or the control of a flow, of energy and/or information amongst physical continuants that are participants in the physical process.

Physical property
type: Class
subclass of: Physical model component
comment: A physical attribute of an instance of a physical entity, an occurrence of a physical process, or a physical dependency that has a quantitative value that is measurable by a physical device or method, or is computable from such values.

Real
type: Class
subclass of: Data structure
comment: A data structure whose value is limited to the real numbers.

Reference physical dependency
type: Class
subclass of: Physical dependency
comment: A physical dependency that is defined using a term in an external knowledge resource.

Reference physical entity
type: Class
subclass of: Physical entity
comment: A physical entity that is defined using a term from an external knowledge resource.

Reference physical process
type: Class
subclass of: Physical process
comment: A physical process that is defined using a term in an external knowledge resource.

Reference physical property
type: Class
subclass of: Physical property
comment: A physical property that is defined using a term in an external knowledge resource.

Relational constraint
type: Class
subclass of: Computational model component
comment: A logical expression that constrains, but does not define, the value of a data structure. Example: x > 0.

SemSim component
type: Class
comment: A computational or physical element of a SemSim model.

Submodel
type: Class
subclass of: Physical model component
comment: A grouping of one or more data structures that comprise a computationally or physically distinct part of a model or submodel.

Unit of measurement
type: Class
subclass of: Computational model component
comment: A physical quantity chosen as a standard in terms of which other physical quantities may be expressed.

http://www.bhi.washington.edu/SemSim/23032015175934459m0500#B
type: NamedIndividual
type: Submodel
name: B
has associated data structure: B.B
has associated data structure: B.Cp
has associated data structure: B.F
has associated data structure: B.K2
has associated data structure: B.n2
has computational component: B computation

B.B
type: NamedIndividual
type: Decimal
metadata ID: B_B
is discrete: false
is solution domain: false
has cell m lpublic interface: out
is declared: true
comment: Bound concentration of methadone
is computational component for: Chemical concentration
mapped to: R.B
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
has computational component: B.B
physical property of: Bound Methadone

B.Cp
type: NamedIndividual
type: Decimal
is discrete: false
is solution domain: false
has cell m lpublic interface: in
is declared: true
comment: Arterial blood concentration of methadone
is computational component for: Chemical concentration
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
has computational component: B.Cp
physical property of: Free Methadone

B.F
type: NamedIndividual
type: Decimal
has start value: 0.48
metadata ID: B_F
is solution domain: false
is discrete: false
has cell m lpublic interface: out
is declared: true
comment: Free methadone concentration in plasma
is computational component for: Chemical concentration
mapped to: R.F
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
has computational component: B.F
physical property of: Free Methadone

B.K2
type: NamedIndividual
type: Decimal
has start value: 0.8532
metadata ID: B_K2
is discrete: false
is solution domain: false
is declared: true
comment: Binding Constant
is computational component for: B.K2 property
has unit: UNIT per micromolar

B.n2
type: NamedIndividual
type: Decimal
has start value: 1
metadata ID: B_n2
is solution domain: false
is discrete: false
is declared: true
comment: Number of non-competitive binding sites on the protein molecule
is computational component for: B.n2 property

B computation
type: NamedIndividual
type: Computation
has math ML: <apply> <eq /> <ci>B</ci> <apply> <divide /> <apply> <times /> <ci>F</ci> <ci>n2</ci> <ci>K2</ci> <ci>Cp</ci> </apply> <apply> <plus /> <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn> <apply> <times /> <ci>K2</ci> <ci>F</ci> </apply> </apply> </apply> </apply>
is computational component for: http://www.bhi.washington.edu/SemSim/23032015175934459m0500#B

Bound Methadone
type: NamedIndividual
type: methadone
type: Custom physical entity
has physical property: Chemical concentration
is index entity for: Bound Methadone part of fma62970 part of fma9670
part of: Portion of plasma

http://www.bhi.washington.edu/SemSim/23032015175934459m0500#C
type: NamedIndividual
type: Submodel
name: C
has associated data structure: C.C
has associated data structure: C.Ca
has associated data structure: C.P
has associated data structure: C.Q
has associated data structure: C.R
has associated data structure: C.V
has associated data structure: C.time
has computational component: C computation

C.C
type: NamedIndividual
type: Decimal
has start value: 0
metadata ID: C_C
is discrete: false
is solution domain: false
has cell m lpublic interface: out
is declared: true
comment: Total methadone concentration in the organ's metabolizing tissue
is computational component for: Chemical concentration
mapped to: Cv.C
mapped to: R.C
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
has computational component: C.C
physical property of: methadone

C.Ca
type: NamedIndividual
type: Decimal
is discrete: false
is solution domain: false
has cell m lpublic interface: in
is declared: true
comment: Arterial blood concentration of methadone
is computational component for: Chemical concentration
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
has computational component: C.Ca
physical property of: Free Methadone

C.P
type: NamedIndividual
type: Decimal
is solution domain: false
is discrete: false
has cell m lpublic interface: in
is declared: true
comment: Partition coefficient of organ
is computational component for: C.P property

C.Q
type: NamedIndividual
type: Decimal
is discrete: false
is solution domain: false
has cell m lpublic interface: in
is declared: true
comment: Volumetric blood flow of organ
is computational component for: C.Q property
has unit: UNIT flow

C.R
type: NamedIndividual
type: Decimal
is solution domain: false
is discrete: false
has cell m lpublic interface: in
is declared: true
comment: Metabolic rate of methadone
is computational component for: Chemical concentration flow rate
has unit: UNIT flux

Chemical concentration flow rate
type: NamedIndividual
refers to: Chemical concentration flow rate
has computational component: C.R
physical property of: Metabolism of Methadone in Organ

C.V
type: NamedIndividual
type: Decimal
has start value: 1454
metadata ID: C_V
is discrete: false
is solution domain: false
is declared: true
comment: Volume of organ
is computational component for: Total volume of shape
has unit: UNIT ml

Total volume of shape
type: NamedIndividual
refers to: Total volume of shape
has computational component: C.V
physical property of: Organ

C.time
type: NamedIndividual
type: Decimal
is discrete: false
is solution domain: false
has cell m lpublic interface: in
is declared: true
comment: Time domain
is computational component for: C.time property
has unit: UNIT minute

methadone
type: NamedIndividual
refers to: methadone
has physical property: Chemical concentration
is index entity for: CHEBI 6807 part of Metabolizing Tissue of Organ
part of: Metabolizing Tissue of Organ

methadone
type: NamedIndividual
refers to: methadone
is index entity for: CHEBI 6807 part of fma83067
has physical property: Chemical concentration
part of: Portion of venous blood

methadone
type: NamedIndividual
refers to: methadone
is index entity for: CHEBI 6807 part of fma83066
has physical property: Chemical concentration
part of: Portion of arterial blood

2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
type: NamedIndividual
refers to: 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
is index entity for: CHEBI 80645 part of Metabolizing Tissue of Organ
part of: Metabolizing Tissue of Organ

2-Ethyl-5-methyl-3,3-diphenyl-1-pyrroline
type: NamedIndividual
refers to: 2-Ethyl-5-methyl-3,3-diphenyl-1-pyrroline
is index entity for: CHEBI 80646 part of Metabolizing Tissue of Organ
part of: Metabolizing Tissue of Organ

C computation
type: NamedIndividual
type: Computation
has math ML: <apply> <eq /> <apply> <diff /> <bvar> <ci>time</ci> </bvar> <ci>C</ci> </apply> <apply> <divide /> <apply> <minus /> <apply> <times /> <ci>Q</ci> <apply> <minus /> <ci>Ca</ci> <apply> <divide /> <ci>C</ci> <ci>P</ci> </apply> </apply> </apply> <apply> <times /> <ci>R</ci> <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="ml">1</cn> </apply> </apply> <ci>V</ci> </apply> </apply>
is computational component for: http://www.bhi.washington.edu/SemSim/23032015175934459m0500#C

Ca
type: NamedIndividual
type: Submodel
name: Ca
has associated data structure: Ca.Ca
has associated data structure: Ca.Cv
has associated data structure: Ca.Qc
has associated data structure: Ca.Va
has associated data structure: Ca.Vv
has associated data structure: Ca.time
has computational component: Ca computation

Ca.Ca
type: NamedIndividual
type: Decimal
has start value: 6.6685
metadata ID: Ca_Ca
is discrete: false
is solution domain: false
has cell m lpublic interface: out
is declared: true
comment: Arterial blood concentration of methadone
mapped to: B.Cp
mapped to: C.Ca
is computational component for: Chemical concentration
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
physical property of: methadone
has computational component: Ca.Ca

Ca.Cv
type: NamedIndividual
type: Decimal
is solution domain: false
is discrete: false
has cell m lpublic interface: in
is declared: true
comment: Mixed venous concentration of drug
is computational component for: Chemical concentration
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
physical property of: methadone
has computational component: Ca.Cv

Ca.Qc
type: NamedIndividual
type: Decimal
is discrete: false
is solution domain: false
has cell m lpublic interface: in
is declared: true
comment: Total cardiac output
is computational component for: Ca.Qc property
has unit: UNIT flow

Ca.Va
type: NamedIndividual
type: Decimal
has start value: 2148
metadata ID: Ca_Va
is discrete: false
is solution domain: false
is declared: true
comment: Arterial blood volume
is computational component for: Fluid volume
has unit: UNIT ml

Fluid volume
type: NamedIndividual
refers to: Fluid volume
has computational component: Ca.Va
physical property of: Portion of arterial blood

Ca.Vv
type: NamedIndividual
type: Decimal
has start value: 3431
metadata ID: Ca_Vv
is solution domain: false
is discrete: false
is declared: true
comment: Venous blood volume
is computational component for: Fluid volume
has unit: UNIT ml

Fluid volume
type: NamedIndividual
refers to: Fluid volume
has computational component: Ca.Vv
physical property of: Portion of venous blood

Ca.time
type: NamedIndividual
type: Decimal
is discrete: false
is solution domain: false
has cell m lpublic interface: in
is declared: true
comment: Time domain
is computational component for: Ca.time property
has unit: UNIT minute

Ca computation
type: NamedIndividual
type: Computation
has math ML: <apply> <eq /> <apply> <diff /> <bvar> <ci>time</ci> </bvar> <ci>Ca</ci> </apply> <apply> <divide /> <apply> <times /> <ci>Qc</ci> <apply> <minus /> <ci>Cv</ci> <ci>Ca</ci> </apply> </apply> <apply> <plus /> <ci>Va</ci> <ci>Vv</ci> </apply> </apply> </apply>
is computational component for: Ca

Cv
type: NamedIndividual
type: Submodel
name: Cv
has associated data structure: Cv.C
has associated data structure: Cv.Cv
has associated data structure: Cv.P
has associated data structure: Cv.Q
has associated data structure: Cv.Qc
has computational component: Cv computation

Cv.C
type: NamedIndividual
type: Decimal
is solution domain: false
is discrete: false
has cell m lpublic interface: in
is declared: true
comment: Total methadone concentration in the organ's metabolizing tissue
is computational component for: Chemical concentration
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
physical property of: methadone
has computational component: Cv.C

Cv.Cv
type: NamedIndividual
type: Decimal
metadata ID: Cv_Cv
is solution domain: false
is discrete: false
has cell m lpublic interface: out
is declared: true
comment: Mixed venous concentration of drug
mapped to: Ca.Cv
is computational component for: Chemical concentration
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
physical property of: methadone
has computational component: Cv.Cv

Cv.P
type: NamedIndividual
type: Decimal
is discrete: false
is solution domain: false
has cell m lpublic interface: in
is declared: true
comment: Partition coefficient of organ
is computational component for: Cv.P property

Cv.Q
type: NamedIndividual
type: Decimal
is discrete: false
is solution domain: false
has cell m lpublic interface: in
is declared: true
comment: Volumetric blood flow of organ
is computational component for: Cv.Q property
has unit: UNIT flow

Cv.Qc
type: NamedIndividual
type: Decimal
is solution domain: false
is discrete: false
has cell m lpublic interface: in
is declared: true
comment: Total cardiac output
is computational component for: Cv.Qc property
has unit: UNIT flow

Cv computation
type: NamedIndividual
type: Computation
has math ML: <apply> <eq /> <ci>Cv</ci> <apply> <divide /> <apply> <divide /> <apply> <times /> <ci>Q</ci> <ci>C</ci> </apply> <ci>P</ci> </apply> <ci>Qc</ci> </apply> </apply>
is computational component for: Cv

Free Methadone
type: NamedIndividual
type: methadone
type: Custom physical entity
has physical property: Chemical concentration
is index entity for: Free Methadone part of fma62970
part of: Portion of plasma

Free Methadone
type: NamedIndividual
type: methadone
type: Custom physical entity
has physical property: Chemical concentration
is index entity for: Free Methadone part of fma83066
part of: Portion of arterial blood

Metabolism of Methadone in Organ
type: NamedIndividual
type: Custom physical process
has physical property: Chemical concentration flow rate
has source: methadone
has sink: 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
has sink: 2-Ethyl-5-methyl-3,3-diphenyl-1-pyrroline
has mediator: Organ

Axiom
has multiplier: 1.0
annotated property: hasSource
annotated target: methadone
annotated source: Metabolism of Methadone in Organ

Axiom
has multiplier: 1.0
annotated property: hasSink
annotated target: 2-Ethyl-5-methyl-3,3-diphenyl-1-pyrroline
annotated source: Metabolism of Methadone in Organ

Axiom
has multiplier: 1.0
annotated property: hasSink
annotated target: 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
annotated source: Metabolism of Methadone in Organ

Axiom
has multiplier: 1.0
annotated property: hasMediator
annotated source: Metabolism of Methadone in Organ
annotated target: Organ

Metabolizing Tissue of Organ
type: NamedIndividual
type: Custom physical entity
has part: methadone
has part: 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
has part: 2-Ethyl-5-methyl-3,3-diphenyl-1-pyrroline

http://www.bhi.washington.edu/SemSim/23032015175934459m0500#R
type: NamedIndividual
type: Submodel
name: R
has associated data structure: R.B
has associated data structure: R.C
has associated data structure: R.F
has associated data structure: R.ISF
has associated data structure: R.Km
has associated data structure: R.R
has associated data structure: R.Vmax
has associated data structure: R.age
has associated data structure: R.fu
has computational component: R computation

R.B
type: NamedIndividual
type: Decimal
is discrete: false
is solution domain: false
has cell m lpublic interface: in
is declared: true
comment: Bound concentration of methadone
is computational component for: Chemical concentration
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
physical property of: Bound Methadone
has computational component: R.B

R.C
type: NamedIndividual
type: Decimal
is discrete: false
is solution domain: false
has cell m lpublic interface: in
is declared: true
comment: Total methadone concentration in the organ's metabolizing tissue
is computational component for: Chemical concentration
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
physical property of: methadone
has computational component: R.C

R.F
type: NamedIndividual
type: Decimal
is solution domain: false
is discrete: false
has cell m lpublic interface: in
is declared: true
comment: Free methadone concentration in plasma
is computational component for: Chemical concentration
has unit: UNIT micromolar

Chemical concentration
type: NamedIndividual
refers to: Chemical concentration
physical property of: Free Methadone
has computational component: R.F

R.ISF
type: NamedIndividual
type: Decimal
metadata ID: R_ISF
is solution domain: false
is discrete: false
is declared: true
comment: Scaling factor for scaling adult Vmax to infant Vmax
is computational component for: R.ISF property

R.Km
type: NamedIndividual
type: Decimal
has start value: 198
metadata ID: R_Km
is discrete: false
is solution domain: false
is declared: true
comment: Michaelis-Menten constant
is computational component for: R.Km property
has unit: UNIT micromolar

R.R
type: NamedIndividual
type: Decimal
metadata ID: R_R
is discrete: false
is solution domain: false
has cell m lpublic interface: out
is declared: true
comment: Metabolic rate of methadone
mapped to: C.R
is computational component for: Chemical concentration flow rate
has unit: UNIT flux

Chemical concentration flow rate
type: NamedIndividual
refers to: Chemical concentration flow rate
physical property of: Metabolism of Methadone in Organ
has computational component: R.R

R.Vmax
type: NamedIndividual
type: Decimal
has start value: 9.433e-3
metadata ID: R_Vmax
is solution domain: false
is discrete: false
is declared: true
comment: Michaelis-Menten constant
is computational component for: R.Vmax property
has unit: UNIT flux

R.age
type: NamedIndividual
type: Decimal
has start value: 5
metadata ID: R_age
is solution domain: false
is discrete: false
is declared: true
is computational component for: R.age property

R.fu
type: NamedIndividual
type: Decimal
metadata ID: R_fu
is discrete: false
is solution domain: false
is declared: true
comment: Unbound fraction of methadone
is computational component for: R.fu property

R computation
type: NamedIndividual
type: Computation
has math ML: <apply> <eq /> <ci>R</ci> <apply> <divide /> <apply> <times /> <ci>ISF</ci> <ci>Vmax</ci> <ci>fu</ci> <ci>C</ci> </apply> <apply> <plus /> <ci>Km</ci> <apply> <times /> <ci>fu</ci> <ci>C</ci> </apply> </apply> </apply> </apply> <apply> <eq /> <ci>fu</ci> <apply> <divide /> <ci>F</ci> <apply> <plus /> <ci>F</ci> <ci>B</ci> </apply> </apply> </apply> <apply> <eq /> <ci>ISF</ci> <apply> <plus /> <apply> <minus /> <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">8.3212</cn> </apply> <apply> <times /> <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.0401</cn> <ci>age</ci> </apply> <apply> <times /> <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4.1962</cn> <apply> <log /> <apply> <times /> <ci>age</ci> <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">365</cn> </apply> </apply> </apply> </apply> </apply>
is computational component for: http://www.bhi.washington.edu/SemSim/23032015175934459m0500#R

UNIT flow
type: NamedIndividual
type: Unit of measurement
has computational code: flow
unit for: C.Q
unit for: Ca.Qc
unit for: Cv.Q
unit for: Cv.Qc
has unit factor: UNIT litre
has unit factor: UNIT minute
unit for: model constants.Q
unit for: model constants.Qc

Axiom
has unit factor prefix: milli
annotated property: hasUnitFactor
annotated source: UNIT flow
annotated target: UNIT litre

Axiom
has unit factor exponent: -1.0
annotated property: hasUnitFactor
annotated source: UNIT flow
annotated target: UNIT minute

UNIT flux
type: NamedIndividual
type: Unit of measurement
has computational code: flux
unit for: C.R
unit for: R.R
unit for: R.Vmax
has unit factor: UNIT micromolar
has unit factor: UNIT minute

Axiom
has unit factor exponent: -1.0
annotated property: hasUnitFactor
annotated source: UNIT flux
annotated target: UNIT minute

UNIT litre
type: NamedIndividual
type: Unit of measurement
has computational code: litre
is fundamental unit: true
unit factor for: UNIT flow
unit factor for: UNIT micromolar
unit factor for: UNIT ml

UNIT micromolar
type: NamedIndividual
type: Unit of measurement
has computational code: micromolar
unit for: B.B
unit for: B.Cp
unit for: B.F
unit for: C.C
unit for: C.Ca
unit for: Ca.Ca
unit for: Ca.Cv
unit for: Cv.C
unit for: Cv.Cv
unit for: R.B
unit for: R.C
unit for: R.F
unit for: R.Km
unit factor for: UNIT flux
has unit factor: UNIT litre
has unit factor: UNIT mole
unit factor for: UNIT per micromolar

Axiom
has unit factor exponent: -1.0
annotated property: hasUnitFactor
annotated target: UNIT litre
annotated source: UNIT micromolar

Axiom
has unit factor prefix: micro
annotated property: hasUnitFactor
annotated source: UNIT micromolar
annotated target: UNIT mole

UNIT minute
type: NamedIndividual
type: Unit of measurement
has computational code: minute
unit for: C.time
unit for: Ca.time
unit factor for: UNIT flow
unit factor for: UNIT flux
has unit factor: UNIT second
unit for: environment.time

UNIT ml
type: NamedIndividual
type: Unit of measurement
has computational code: ml
unit for: C.V
unit for: Ca.Va
unit for: Ca.Vv
has unit factor: UNIT litre

Axiom
has unit factor prefix: milli
annotated property: hasUnitFactor
annotated target: UNIT litre
annotated source: UNIT ml

UNIT mole
type: NamedIndividual
type: Unit of measurement
has computational code: mole
is fundamental unit: true
unit factor for: UNIT micromolar

UNIT per micromolar
type: NamedIndividual
type: Unit of measurement
has computational code: per_micromolar
unit for: B.K2
has unit factor: UNIT micromolar

Axiom
has unit factor exponent: -1.0
annotated property: hasUnitFactor
annotated target: UNIT micromolar
annotated source: UNIT per micromolar

UNIT second
type: NamedIndividual
type: Unit of measurement
has computational code: second
is fundamental unit: true
unit factor for: UNIT minute

environment
type: NamedIndividual
type: Submodel
name: environment
has associated data structure: environment.time
has computational component: environment computation

environment.time
type: NamedIndividual
type: Decimal
metadata ID: environment_time
is discrete: false
is solution domain: false
has cell m lpublic interface: out
is declared: true
comment: Time domain
mapped to: C.time
mapped to: Ca.time
has unit: UNIT minute
is computational component for: environment.time property

Portion of plasma
type: NamedIndividual
refers to: Portion of plasma
has part: Bound Methadone
is index entity for: fma62970 part of fma9670
part of: Portion of blood

Portion of plasma
type: NamedIndividual
refers to: Portion of plasma
has part: Free Methadone

Organ
type: NamedIndividual
refers to: Organ
has physical property: Total volume of shape

Portion of arterial blood
type: NamedIndividual
refers to: Portion of arterial blood
has part: methadone
has physical property: Fluid volume
has part: Free Methadone

Portion of venous blood
type: NamedIndividual
refers to: Portion of venous blood
has part: methadone
has physical property: Fluid volume

Portion of blood
type: NamedIndividual
refers to: Portion of blood
has part: Portion of plasma

model constants
type: NamedIndividual
type: Submodel
name: model_constants
has associated data structure: model constants.P
has associated data structure: model constants.Q
has associated data structure: model constants.Qc
has computational component: model constants computation

model constants.P
type: NamedIndividual
type: Decimal
has start value: 15.61
is solution domain: false
is discrete: false
metadata ID: model_constants_P
has cell m lpublic interface: out
is declared: true
comment: Partition coefficient of organ
mapped to: C.P
mapped to: Cv.P
is computational component for: model constants.P property

model constants.Q
type: NamedIndividual
type: Decimal
has start value: 1221.34
is discrete: false
is solution domain: false
metadata ID: model_constants_Q
has cell m lpublic interface: out
is declared: true
comment: Volumetric blood flow of organ
mapped to: C.Q
mapped to: Cv.Q
has unit: UNIT flow
is computational component for: model constants.Q property

model constants.Qc
type: NamedIndividual
type: Decimal
has start value: 6445.65
is discrete: false
is solution domain: false
metadata ID: model_constants_Qc
has cell m lpublic interface: out
is declared: true
comment: Total cardiac output
mapped to: Ca.Qc
mapped to: Cv.Qc
has unit: UNIT flow
is computational component for: model constants.Qc property