BIOMD0000000321
type: SBMLModel
units def: 954290
parameter: 274130
length unit: length
modified:
  W3 CDTF: Thu Jun 06 11:58:42 BST 2013
reaction: 274099
species: 274090
parameter: 274128
units def: metaid_0000071
rule: 274114
rule: 274106
units def: 954314
compartment: 274088
compartment: 274086
rule: 274109
time units: metaid_0000071
reaction: 274094
parameter: 274122
reaction: 274097
parameter: 274123
rule: 274105
parameter: 274126
parameter: 274131
parameter: 274119
parameter: 274134
units def: 954254
parameter: 274135
parameter: 274138
rule: 274113
name: Grange2001 - L Dopa PK model
is described by: http://identifiers.org/pubmed/11587490
rule: 274112
substance units: 954230
compartment: 274089
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Vijayalakshmi
    family: Chelliah
parameter: 274118
is version of: GO:0051583
created:
  W3 CDTF: Tue Oct 27 14:45:40 GMT 2009
parameter: 274120
reaction: 274095
volume units: 697232
parameter: 274124
initial assignment: BIOMD0000000321#
parameter: 274132
parameter: 274136
species: 274091
is: MODEL1103250000
rule: 274108
area units: area
reaction: 274098
species: 274092
parameter: 274127
is version of: G20
occurs in: http://identifiers.org/taxonomy/10116
notes: Grange2001 - L-dopa PK model A pharmacokinetics of L-dopa in rats after administration of L-dopa alone (this model: BIOMD0000000321) or L-dopa combined with a peripheral AADC (amino-acid-decarboxylase) inhibitor (BIOMD0000000320) has been studied using noncompartmental analysis. This model is described in the article: A pharmacokinetic model to predict the PK interaction of L-dopa and benserazide in rats. Grange S, Holford NH, Guentert TW Pharmaceutical Research [2001, 18(8):1174-1184] Abstract: PURPOSE: To study the PK interaction of L-dopa/benserazide in rats. METHODS: Male rats received a single oral dose of 80 mg/kg L-dopa or 20 mg/kg benserazide or 80/20 mg/kg L-dopa/benserazide. Based on plasma concentrations the kinetics of L-dopa, 3-O-methyldopa (3-OMD), benserazide, and its metabolite Ro 04-5127 were characterized by noncompartmental analysis and a compartmental model where total L-dopa clearance was the sum of the clearances mediated by amino-acid-decarboxylase (AADC), catechol-O-methyltransferase and other enzymes. In the model Ro 04-5127 inhibited competitively the L-dopa clearance by AADC. RESULTS: The coadministration of L-dopa/benserazide resulted in a major increase in systemic exposure to L-dopa and 3-OMD and a decrease in L-dopa clearance. The compartmental model allowed an adequate description of the observed L-dopa and 3-OMD concentrations in the absence and presence of benserazide. It had an advantage over noncompartmental analysis because it could describe the temporal change of inhibition and recovery of AADC. CONCLUSIONS: Our study is the first investigation where the kinetics of benserazide and Ro 04-5127 have been described by a compartmental model. The L-dopa/benserazide model allowed a mechanism-based view of the L-dopa/benserazide interaction and supports the hypothesis that Ro 04-5127 is the primary active metabolite of benserazide. The model has a species (A-dopa) whose initial concentration is calculated from a listOfInitialAssignment…
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Lukas
    family: Endler
parameter: 274139
units def: 954230
rule: 274110
parameter: 274116
curated: true
reaction: 274093

954290
type: SBMLUnitsDef
unit: 954302
name: per_h

954302
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND

274130
type: Parameter
notes: L-Dopa clearance by AADC
is: SBO:0000035
constant: false
units: 954314
value: NaN

954314
type: SBMLUnitsDef
unit: 954338
unit: 954326
name: l_per_h

954338
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND

954326
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exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

274099
type: Reaction
kinetic law: 954531
reactant: 954518
has version: GO:0007588
has version: GO:0042737
is: SBO:0000179
fast: false
reversible: false
name: 3-OMD clearance

954518
type: SpeciesReference
stoichiometry: 1.0
species: 274092

274092
type: Species
notes: amount of 3-OMD in the central compartment
initial concentration: 0.0
constant: false
in compartment: 274089
is version of: CHEBI:25212
name: C_3-OMD
is: SBO:0000247
is: http://identifiers.org/pubchem.compound/9307
has only substance units: false
initial amount: NaN
boundary condition: false

274089
type: Compartment
is version of: FMA:7563
is: SBO:0000290
constant: true
size: 0.196
spatial dimensions: 3.0

274090
type: Species
initial amount: NaN
initial concentration: NaN
notes: amount of L-Dopa in the gut
constant: false
is: http://identifiers.org/pubchem.compound/6047
in compartment: 274086
is: CHEBI:15765
is: SBO:0000247
boundary condition: false
is version of: C00355
has only substance units: true

274086
type: Compartment
is version of: BTO:0000648
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0

274128
type: Parameter
is: SBO:0000381
constant: true
units: dimensionless
value: 0.1

metaid_0000071
type: SBMLUnitsDef
unit: 954350
name: hours

954350
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 3600.0
kind: SECOND

274088
type: Compartment
is version of: FMA:7563
is: SBO:0000290
constant: true
size: 0.496
spatial dimensions: 3.0
name: V_L_Dopa

274094
type: Reaction
kinetic law: 954422
reactant: 954410
is: GO:0030421
has version: GO:0042737
is: SBO:0000179
fast: false
reversible: false
name: hepatic and blood L-Dopa clearance

954410
type: SpeciesReference
stoichiometry: 1.0
species: 274090

274122
type: Parameter
notes: hepatic blood flow
is: SBO:0000002
constant: true
value: 0.828

274097
type: Reaction
is: SBO:0000214
name: L-Dopa clearance via COMT
reactant: 954458
is version of: GO:0042737
fast: false
kinetic law: 954482
is version of: http://identifiers.org/ec-code/2.1.1.6
reversible: false
product: 954470

954458
type: SpeciesReference
stoichiometry: 1.0
species: 274091

274091
type: Species
boundary condition: false
constant: false
is: http://identifiers.org/pubchem.compound/6047
has only substance units: false
is: SBO:0000247
initial concentration: 0.0
is: C00355
notes: amount of L-Dopa in the central compartment
initial amount: NaN
is: CHEBI:15765
in compartment: 274088

954470
type: SpeciesReference
stoichiometry: 1.0
species: 274092

274123
type: Parameter
notes: hepatically cleared fraction of l-dopa
is: SBO:0000381
constant: true
units: dimensionless
value: 0.13

274126
type: Parameter
is: SBO:0000381
constant: false
units: dimensionless
value: NaN

274131
type: Parameter
notes: L-Dopa clearance via unspecified elimination pathways
is: SBO:0000035
constant: false
units: 954314
value: NaN

274119
type: Parameter
notes: gastro-intestinal bioavailability of L-Dopa
is: SBO:0000381
constant: true
units: dimensionless
value: 0.24

274134
type: Parameter
notes: total clearance of L-Dopa
is: SBO:0000035
constant: true
units: 954314
value: 0.823

954254
type: SBMLUnitsDef
unit: 954278
unit: 954266
name: micromole_per_kg

954278
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exponent: -1.0
scale: 0
multipler: 1.0
kind: KILOGRAM

954266
type: SBMLUnit
exponent: 1.0
scale: -9
multipler: 1.0
kind: MOLE

274135
type: Parameter
notes: absorption rate constant of L_DOPA in the gut
is: SBO:0000035
constant: true
units: 954290
value: 2.11

274138
type: Parameter
is: SBO:0000197
constant: true
value: 404.0

954230
type: SBMLUnitsDef
unit: 954242
name: micromole

954242
type: SBMLUnit
exponent: 1.0
scale: -9
multipler: 1.0
kind: MOLE

274118
type: Parameter
notes: hepatic bioavailability of L-Dopa
is: SBO:0000381
constant: false
units: dimensionless
value: NaN

274120
type: Parameter
notes: hepatic blood clearance of L-Dopa
is: SBO:0000035
constant: false
units: 954314
value: NaN

274095
type: Reaction
name: L-Dopa clearance via AADC
is version of: http://identifiers.org/ec-code/4.1.1.28
reactant: 954434
is version of: REACT 15382.1
is version of: GO:0042737
kinetic law: 954446
is: SBO:0000399
fast: false
reversible: false

954434
type: SpeciesReference
stoichiometry: 1.0
species: 274091

274124
type: Parameter
notes: total clearance speed of L-Dopa
is: SBO:0000035
constant: false
units: 954314
value: NaN

274132
type: Parameter
notes: catechol-O-methyltransferase mediated L-Dopa clearance
is: SBO:0000035
constant: false
units: 954314
value: NaN

274136
type: Parameter
is: SBO:0000035
constant: true
value: 0.012
name: CL_3_OMD

274098
type: Reaction
kinetic law: 954506
reactant: 954494
has version: GO:0042737
has version: GO:0007588
is: SBO:0000179
fast: false
reversible: false
name: rest clearance of L-Dopa

954494
type: SpeciesReference
stoichiometry: 1.0
species: 274091

274127
type: Parameter
is: SBO:0000381
constant: true
units: dimensionless
value: 0.69

274139
type: Parameter
is: SBO:0000002
constant: true
value: 0.25

274116
type: Parameter
notes: bioavailability of L-Dopa
is: SBO:0000381
constant: false
units: dimensionless
value: NaN

274093
type: Reaction
kinetic law: 954398
product: 954386
reactant: 954374
is version of: GO:0050892
is: SBO:0000185
fast: false
reversible: false
name: L_Dopa absorption from gut

954386
type: SpeciesReference
stoichiometry: 1.0
species: 274091

954374
type: SpeciesReference
stoichiometry: 1.0
species: 274090