945761
stoichiometry: 1.0
species: 040948
type: SpeciesReference

040962
kinetic law: 945677
reactant: 945665
is: GO:0030421
has version: GO:0042737
is: SBO:0000179
fast: false
reversible: false
name: hepatic and blood L-Dopa clearance
type: Reaction

040947
is: SBO:0000247
is: CHEBI:15765
is: C00355
type: Species
in compartment: 040935
boundary condition: false
initial amount: NaN
is: http://identifiers.org/pubchem.compound/6047
has only substance units: true
initial concentration: NaN
constant: false

945689
stoichiometry: 1.0
species: 040949
type: SpeciesReference

041024
notes: L-Dopa clearance by AADC
is: SBO:0000035
constant: false
units: 945531
value: NaN
type: Parameter

041018
notes: total clearance speed of L-Dopa
is: SBO:0000035
constant: false
units: 945531
value: NaN
type: Parameter

040937
is version of: FMA:7563
is: SBO:0000290
constant: true
size: 0.128
spatial dimensions: 3.0
type: Compartment

946016
stoichiometry: 1.0
species: 040954
type: SpeciesReference

040957
type: Species
initial amount: NaN
is: D03082
constant: false
in compartment: 040940
initial concentration: 0.0
boundary condition: false
is: http://identifiers.org/pubchem.compound/2327
notes: Benserazide in the central compartment
is: SBO:0000247
has only substance units: false

040972
kinetic law: 945859
reactant: 945846
has version: GO:0007588
has version: GO:0042737
is: SBO:0000179
fast: false
reversible: false
name: rest clearance of L-Dopa
type: Reaction

040952
type: Species
is: SBO:0000247
is: http://identifiers.org/pubchem.compound/9307
boundary condition: false
has only substance units: false
is version of: CHEBI:25212
initial amount: NaN
initial concentration: 0.0
constant: false
in compartment: 040937
name: C_3-OMD

041045
is: SBO:0000035
constant: true
units: 945531
value: 0.072
type: Parameter

ORG:
  orgname: EMBL-EBI
n:
  given: Vijayalakshmi
  family: Chelliah

041039
is: SBO:0000035
constant: true
units: 945531
value: 0.00895
name: CL_3_OMD
type: Parameter

041038
notes: oral bioavailability of Benserazide
is: SBO:0000381
constant: true
units: dimensionless
value: 0.022
type: Parameter

945555
exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

945992
stoichiometry: 1.0
species: 040960
type: SpeciesReference

040948
is: http://identifiers.org/pubchem.compound/2327
in compartment: 040935
has only substance units: true
initial amount: NaN
is: SBO:0000247
constant: false
type: Species
boundary condition: false
initial concentration: NaN
is: D03082

041011
notes: hepatic bioavailability of L-Dopa
is: SBO:0000381
constant: false
units: dimensionless
value: NaN
type: Parameter

040980
kinetic law: 945968
reactant: 945956
has version: GO:0042737
has version: GO:0007588
is: SBO:0000179
fast: false
reversible: false
name: ro 04-5127 clearance
type: Reaction

040971
is version of: GO:0042737
kinetic law: 945834
product: 945822
reactant: 945810
name: L-Dopa clearance via COMT
fast: false
reversible: false
is version of: http://identifiers.org/ec-code/2.1.1.6
is: SBO:0000214
type: Reaction

040951
initial amount: NaN
constant: false
is: http://identifiers.org/pubchem.compound/6047
is: C00355
boundary condition: false
is: CHEBI:15765
type: Species
initial concentration: 0.0
is: SBO:0000247
has only substance units: false
in compartment: 040936

945701
stoichiometry: 1.0
species: 040954
type: SpeciesReference

040941
is version of: FMA:76700
is: SBO:0000290
constant: true
size: 0.127
spatial dimensions: 3.0
type: Compartment

041044
is: SBO:0000035
constant: true
units: 945531
value: 4.29
type: Parameter

041030
is: SBO:0000288
constant: true
value: 0.00246
type: Parameter

040961
kinetic law: 945653
product: 945640
reactant: 945628
is version of: GO:0050892
is: SBO:0000185
fast: false
reversible: false
name: L_Dopa absorption from gut
type: Reaction

040968
kinetic law: 945773
reactant: 945761
is: GO:0030421
has version: GO:0042737
is: SBO:0000179
fast: false
reversible: false
name: benserazide clearance from gut
type: Reaction

945640
stoichiometry: 1.0
species: 040951
type: SpeciesReference

945956
stoichiometry: 1.0
species: 040954
type: SpeciesReference

040974
kinetic law: 945883
reactant: 945871
has version: GO:0042737
has version: GO:0007588
is: SBO:0000179
fast: false
reversible: false
name: 3-OMD clearance
type: Reaction

041012
notes: gastro-intestinal bioavailability of L-Dopa
is: SBO:0000381
constant: true
units: dimensionless
value: 1.0
type: Parameter

040935
is version of: BTO:0000648
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0
type: Compartment

040949
initial amount: NaN
is: http://identifiers.org/pubchem.compound/188973
is: SBO:0000247
constant: false
has only substance units: true
type: Species
boundary condition: false
is version of: CHEBI:25212
initial concentration: NaN
in compartment: 040935

040954
is: SBO:0000247
is: http://identifiers.org/pubchem.compound/188973
notes: Ro 04-5127, an inhibitor of amino-acid carboxylase (AADC), in the central compartment
in compartment: 040943
boundary condition: false
is version of: CHEBI:25212
initial amount: NaN
has only substance units: false
constant: false
initial concentration: 0.0
type: Species

041033
notes: absorption rate constant of L_DOPA in the gut
is: SBO:0000035
constant: true
value: 1.29
type: Parameter

945737
stoichiometry: 1.0
species: 040957
type: SpeciesReference

040981
kinetic law: 946004
product: 945992
reactant: 945980
is: SBO:0000185
fast: false
reversible: true
name: benserazide distribution
type: Reaction

BIOMD0000000320
reaction: 040961
units def: 945531
reaction: 040969
compartment: 040943
occurs in: http://identifiers.org/taxonomy/10116
parameter: 041017
parameter: 041023
is: MODEL0910130001
parameter: 041027
rule: 040997
reaction: 040971
is version of: GO:0051583
compartment: 040946
compartment: 040936
units def: 945507
time units: metaid_0000071
reaction: 040974
area units: area
reaction: 040965
initial assignment: BIOMD0000000320#
species: 040957
notes: Grange2001 - PK interaction of L-dopa and benserazide A pharmacokinetics of L-dopa in rats after administration of L-dopa alone (BIOMD0000000321) or L-dopa combined with a peripheral AADC (amino-acid-decarboxylase) inhibitor (this model: 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 volumes and variables in this model are taken for a rat with 0.25 kg. The in…
parameter: 041045
parameter: 041041
species: 040947
parameter: 041036
reaction: 040980
parameter: 041021
parameter: 041012
name: Grange2001 - PK interaction of L-dopa and benserazide
volume units: 697232
parameter: 041050
parameter: 041051
units def: metaid_0000071
rule: 041006
rule: 040995
species: 040952
parameter: 041026
rule: 040998
parameter: 041039
rule: 041003
reaction: 040968
parameter: 041054
compartment: 040935
parameter: 041029
parameter: 041030
compartment: 040941
type: SBMLModel
parameter: 041044
units def: 945470
parameter: 041020
species: 040948
curated: true
reaction: 040963
reaction: 040978
rule: 041000
species: 040955
parameter: 041035
parameter: 041009
reaction: 040983
parameter: 041038
rule: 041007
parameter: 041011
parameter: 041014
parameter: 041015
parameter: 041053
is described by: http://identifiers.org/pubmed/11587490
compartment: 040937
species: 040960
reaction: 040962
compartment: 040940
is version of: G20
reaction: 040972
parameter: 041032
rule: 041004
parameter: 041033
species: 040949
reaction: 040981
parameter: 041018
length unit: length

040955
in compartment: 040946
type: Species
initial concentration: 0.0
is version of: CHEBI:25212
initial amount: NaN
boundary condition: false
constant: false
notes: Ro 04-5127 in the peripheral compartment
has only substance units: false
is: http://identifiers.org/pubchem.compound/188973
is: SBO:0000247

040960
initial concentration: 0.0
boundary condition: false
has only substance units: false
initial amount: NaN
is: D03082
type: Species
in compartment: 040941
is: http://identifiers.org/pubchem.compound/2327
is: SBO:0000247
notes: Benserazide in the peripheral compartment
constant: false

040969
is version of: REACT 15382.1
kinetic law: 945798
is version of: http://identifiers.org/ec-code/4.1.1.28
reactant: 945785
is version of: GO:0042737
is: SBO:0000399
name: L-Dopa clearance via AADC
fast: false
type: Reaction
reversible: false

945785
stoichiometry: 1.0
species: 040951
type: SpeciesReference

040940
is version of: FMA:76700
is: SBO:0000290
constant: true
size: 0.202
spatial dimensions: 3.0
type: Compartment

945567
exponent: 1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

041023
is: SBO:0000381
constant: true
units: dimensionless
value: 0.1
type: Parameter

945822
stoichiometry: 1.0
species: 040952
type: SpeciesReference

945871
stoichiometry: 1.0
species: 040952
type: SpeciesReference

945920
stoichiometry: 1.0
species: 040957
type: SpeciesReference

metaid_0000071
unit: 945567
name: hours
type: SBMLUnitsDef

040936
is version of: FMA:7563
is: SBO:0000290
constant: true
size: 0.496
spatial dimensions: 3.0
name: V_L_Dopa
type: Compartment

041032
notes: total clearance of L-Dopa wo. inhibition
is: SBO:0000035
constant: true
units: 945531
value: 0.823
type: Parameter

041042
is: SBO:0000381
constant: true
units: dimensionless
value: 0.15
type: Parameter

041020
is: SBO:0000381
constant: false
units: dimensionless
value: NaN
type: Parameter

040943
is version of: FMA:76700
is: SBO:0000290
constant: true
size: 0.0691
spatial dimensions: 3.0
type: Compartment

040983
kinetic law: 946040
product: 946028
reactant: 946016
is: SBO:0000185
fast: false
reversible: true
name: ro 04-5127 distribution
type: Reaction

945482
exponent: 1.0
scale: -9
multipler: 1.0
kind: MOLE
type: SBMLUnit

041014
notes: hepatic blood clearance of L-Dopa
is: SBO:0000035
constant: false
units: 945531
value: NaN
type: Parameter

041035
notes: absorption rate constant of Ro 04-5127
is: SBO:0000035
constant: true
value: 2.47
name: ka_m
type: Parameter

945507
unit: 945519
name: per_h
type: SBMLUnitsDef

945531
unit: 945555
unit: 945543
name: l_per_h
type: SBMLUnitsDef

041029
notes: uninhibited AADC clearance velocity
is: SBO:0000035
constant: false
units: 945531
value: NaN
type: Parameter

041053
is: SBO:0000196
constant: true
units: 945445
value: NaN
type: Parameter

041054
notes: Ro04-5127 fraction of Bensarazide in gut
is: SBO:0000381
constant: true
value: 0.07
name: Bens_Ro04-5127_fraction_gut
type: Parameter

945725
stoichiometry: 1.0
species: 040948
type: SpeciesReference

041021
is: SBO:0000381
constant: true
units: dimensionless
value: 0.69
type: Parameter

040965
kinetic law: 945749
product: 945737
reactant: 945725
is version of: GO:0050892
is: SBO:0000185
fast: false
reversible: false
name: benserazide absorption from gut
type: Reaction

945932
stoichiometry: 1.0
species: 040954
type: SpeciesReference

945665
stoichiometry: 1.0
species: 040947
type: SpeciesReference

041015
notes: hepatic blood flow
is: SBO:0000002
constant: true
value: 0.828
type: Parameter

041048
is: SBO:0000197
constant: true
units: 945470
value: 404.0
type: Parameter

041009
notes: bioavailability of L-Dopa
is: SBO:0000381
constant: false
units: dimensionless
value: NaN
type: Parameter

945519
exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

945495
exponent: -1.0
scale: 0
multipler: 1.0
kind: KILOGRAM
type: SBMLUnit

945470
unit: 945495
unit: 945482
name: micromole_per_kg
type: SBMLUnitsDef

040978
kinetic law: 945944
product: 945932
reactant: 945920
is version of: GO:0042737
is: SBO:0000211
fast: false
reversible: false
name: benserazide metabolism to ro 04-5127
type: Reaction

945445
unit: 945458
name: micromole
type: SBMLUnitsDef

945628
stoichiometry: 1.0
species: 040947
type: SpeciesReference

041050
is: SBO:0000197
constant: true
units: 945470
value: 78.0
type: Parameter

945980
stoichiometry: 1.0
species: 040957
type: SpeciesReference

945543
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

041047
is: SBO:0000035
constant: true
units: 945531
value: 1.06
type: Parameter

945810
stoichiometry: 1.0
species: 040951
type: SpeciesReference

946028
stoichiometry: 1.0
species: 040955
type: SpeciesReference

041026
notes: L-dopa clearance via unspecified elimination pathways
is: SBO:0000035
constant: false
units: 945531
value: NaN
type: Parameter

041041
is: SBO:0000035
constant: true
units: 945531
value: 1.67
type: Parameter

945896
stoichiometry: 1.0
species: 040957
type: SpeciesReference

040977
kinetic law: 945908
reactant: 945896
has version: GO:0042737
has version: GO:0007588
is: SBO:0000179
fast: false
reversible: false
name: benserazide clearance
type: Reaction

041017
notes: hepatically cleared fraction of l-dopa
is: SBO:0000381
constant: true
units: dimensionless
value: 0.13
type: Parameter

040946
is version of: FMA:76700
is: SBO:0000290
constant: true
size: 3.2
spatial dimensions: 3.0
type: Compartment

040963
kinetic law: 945713
product: 945701
reactant: 945689
is version of: GO:0050892
is: SBO:0000185
fast: false
reversible: false
name: ro 04-5127 absorption from gut
type: Reaction

041051
is: SBO:0000002
constant: true
units: kilogram
value: 0.25
type: Parameter

945458
exponent: 1.0
scale: -9
multipler: 1.0
kind: MOLE
type: SBMLUnit

041027
notes: catechol-O-methyltransferase mediated L-Dopa clearance
is: SBO:0000035
constant: false
units: 945531
value: NaN
type: Parameter

945846
stoichiometry: 1.0
species: 040951
type: SpeciesReference

041036
notes: absorption rate constant of benserazide
is: SBO:0000035
constant: true
value: 0.94
name: ka_b
type: Parameter

orgname: EMBL-EBI

given: Lukas
family: Endler

W3 CDTF: Mon May 20 15:25:05 BST 2013

W3 CDTF: Tue Oct 27 14:45:40 GMT 2009