BIOMD0000000241
type: SBMLModel
parameter: metaid_0000022
units def: metaid_0000041
rule: metaid_0000029
compartment: metaid_0000003
modified:
  W3 CDTF: Tue Jun 21 13:46:00 BST 2011
compartment: metaid_0000007
is version of: GO:0008217
species: metaid_0000009
parameter: metaid_0000021
species: metaid_0000011
created:
  W3 CDTF: Fri Jan 08 11:00:59 GMT 2010
units def: metaid_1000044
parameter: metaid_0000028
parameter: metaid_0000014
substance units: metaid_0000039
units def: metaid_0000045
rule: metaid_0000030
parameter: metaid_0000036
event: metaid_0000037
parameter: metaid_0000038
rule: metaid_0000033
units def: metaid_0000040
parameter: metaid_0000035
length unit: length
name: Shi1993_Caffeine_pressor_tolerance
parameter: metaid_0000020
is: MODEL1001080000
rule: metaid_0000034
species: metaid_0000012
parameter: metaid_0000017
occurs in: http://identifiers.org/taxonomy/9606
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Lukas
    family: Endler
parameter: metaid_0000019
notes: described in: Pharmacokinetic-pharmacodynamic modeling of caffeine: Tolerance to pressor effects Shi J, Benowitz NL, Denaro CP and Sheiner LB. ; Clin. Pharmacol. Ther. 1993 Jan;53(1):6-14. PMID: 8422743 ; Abstract: We propose a parametric pharmacokinetic-pharmacodynamic model for caffeine that quantifies the development of tolerance to the pressor effect of the drug and characterizes the mean behavior and inter-individual variation of both pharmacokinetics and pressor effect. Our study in a small group of subjects indicates that acute tolerance develops to the pressor effect of caffeine and that both the pressor effect and tolerance occur after some time delay relative to changes in plasma caffeine concentration. The half-life of equilibration of effect with plasma caffeine concentration is about 20 minutes. The half-life of development and regression of tolerance is estimated to be about 1 hour, and the model suggests that tolerance, at its fullest, causes more than a 90 percent reduction of initial (nontolerant) effect. Whereas tolerance to the pressor effect of caffeine develops in habitual coffee drinkers, the pressor response is regained after relatively brief periods of abstinence. Because of the rapid development and regression of tolerance, the pressor response to caffeine depends on how much caffeine is consumed, the schedule of consumption, and the elimination half-life of caffeine. Caffeine intake in this version is modelled as cups of coffee drunk at regular intervals (parameter t_interval ). The amount of caffeine per cup is determined by the parameter cupsize . The body weight of the person drinking is given by the parameter bodyweight . The even coffee cup occures delayed to the drinking of each cup, as the availability of the caffeine in the digestive tract is assumed to be delayed to the ingestion by the time t_lag . This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2011 The BioModels.n…
curated: true
units def: metaid_0000044
parameter: metaid_0000025
parameter: metaid_0000027
parameter: metaid_0100039
parameter: metaid_0000024
rule: metaid_0000031
parameter: metaid_0000026
is version of: GO:0031000
units def: metaid_0000039
area units: metaid_0000005
compartment: metaid_0000005
species: metaid_0000013
compartment: metaid_0000004
compartment: metaid_0000008
parameter: metaid_0000016
volume units: metaid_0000003
units def: metaid_0000043
is described by: http://identifiers.org/pubmed/8422743
parameter: metaid_0000018
parameter: metaid_0000015
species: metaid_0000010
time units: metaid_0000040
units def: metaid_0000042
parameter: metaid_0000023
rule: metaid_0000032

metaid_0000022
type: Parameter
notes: bioavailability
constant: true
value: 0.984
name: F

metaid_0000041
type: SBMLUnitsDef
unit: 736534
name: per_hour

736534
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND

metaid_0000003
type: Compartment
notes: gut compartment, the digestive tract
is version of: FMA:71132
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0
name: Gut

metaid_0000007
type: Compartment
notes: virtual compartment to account for tolerance effects
is: SBO:0000289
constant: true
size: 1.0
spatial dimensions: 3.0
name: Tol

metaid_0000009
type: Species
initial amount: 0.0
boundary condition: false
name: X_gut
is: SBO:0000241
substance units: metaid_0000045
is: C07481
initial concentration: NaN
constant: false
has only substance units: true
is: CHEBI:27732
in compartment: metaid_0000003

metaid_0000045
type: SBMLUnitsDef
unit: 736644
name: mg_per_kg

736644
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: DIMENSIONLESS

metaid_0000021
type: Parameter
constant: true
units: metaid_0000040
value: 3.98
name: t_half

metaid_0000040
type: SBMLUnitsDef
unit: 736522
name: hr

736522
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 3600.0
kind: SECOND

metaid_0000011
type: Species
boundary condition: false
name: C_per
has only substance units: false
is: SBO:0000247
constant: false
is: C07481
in compartment: metaid_0000005
initial concentration: 0.0
initial amount: NaN
is: CHEBI:27732

metaid_0000005
type: Compartment
notes: peripheral compartment
is part of: FMA:20394
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0
name: P

metaid_1000044
type: SBMLUnitsDef
unit: 736632
unit: 736619
name: mg/l

736632
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE

736619
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: KILOGRAM

metaid_0000028
type: Parameter
notes: effect (mean arterial pressure, MAP)
constant: false
units: metaid_0000043
value: NaN
name: MAP

metaid_0000043
type: SBMLUnitsDef
unit: 736571
notes: unit for blood pressure
name: mm_Hg

736571
type: SBMLUnit
exponent: 1.0
scale: -3
multipler: 1.0
kind: METRE

metaid_0000014
type: Parameter
notes: overall clearance per kilogram bodyweight
constant: true
value: 0.11
name: CL

metaid_0000039
type: SBMLUnitsDef
unit: 736510
name: mg

736510
type: SBMLUnit
exponent: 1.0
scale: -6
multipler: 1.0
kind: KILOGRAM

metaid_0000036
type: Parameter
notes: amount of caffeine per cup
constant: true
units: metaid_0000039
value: 90.0
name: cupsize

metaid_0000037
type: Event
event assignment: 736680
event assignment: 736668
trigger: 736656
notes: availability of caffeine in gut after drinking a cup
use values from trigger time: true
name: coffee cup

metaid_0000038
type: Parameter
notes: number of cups drank at time t
constant: false
units: dimensionless
value: 0.0
name: cups

736656
type: Trigger
persistant: true
initial value: true

metaid_0000035
type: Parameter
notes: intervall between drinking of cups of coffee
constant: true
units: metaid_0000040
value: 2.0
name: t_intervall

metaid_0000020
type: Parameter
notes: peripheral to central compartment transport rate
constant: true
units: metaid_0000041
value: 1.19
name: k21

metaid_0000012
type: Species
is version of: CHEBI:27732
constant: false
notes: hypothetical effect-site concentration
initial concentration: 0.0
has only substance units: false
name: C_e
initial amount: NaN
boundary condition: false
is: SBO:0000241
in compartment: metaid_0000008

metaid_0000008
type: Compartment
notes: virtual effect compartment
is: SBO:0000289
constant: true
size: 1.0
spatial dimensions: 3.0
name: Eff

metaid_0000017
type: Parameter
notes: time lag between drinking of coffee and arrival in gastrointestinal tract
constant: true
units: metaid_0000040
value: 0.15
name: t_lag

metaid_0000019
type: Parameter
notes: central to peripheral transport rate
constant: true
units: metaid_0000041
value: 1.64
name: k12

metaid_0000044
type: SBMLUnitsDef
unit: 736607
unit: 736595
unit: 736583
name: mm_Hg per (mg/l)

736607
type: SBMLUnit
exponent: -1.0
scale: -6
multipler: 1.0
kind: KILOGRAM

736595
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

736583
type: SBMLUnit
exponent: 1.0
scale: -3
multipler: 1.0
kind: METRE

metaid_0000025
type: Parameter
notes: base line effect (base MAP)
constant: true
units: metaid_0000043
value: 83.3
name: E_0

metaid_0000027
type: Parameter
constant: true
units: metaid_1000044
value: 0.26
name: T_50

metaid_0100039
type: Parameter
notes: total body weight
constant: true
units: kilogram
value: 80.0
name: bodyweight

metaid_0000024
type: Parameter
notes: first order rate constant of appearance/disappearance of tolerance
constant: true
units: metaid_0000041
value: 0.75
name: k_tol

metaid_0000026
type: Parameter
constant: true
units: metaid_0000044
value: 19.07
name: S

metaid_0000013
type: Species
constant: false
boundary condition: false
notes: hypothetical antagonistic metabolite to account for tolerance development
name: C_t
has only substance units: false
initial amount: NaN
in compartment: metaid_0000007
is: SBO:0000241
initial concentration: 0.0
is version of: CHEBI:27732

metaid_0000004
type: Compartment
notes: the central compartment, corresponding mainly to the plasma. Its apparant volume is given by the parameterV_C
is version of: FMA:62970
is: SBO:0000290
constant: true
size: 0.31
spatial dimensions: 3.0
name: C

metaid_0000016
type: Parameter
constant: true
units: metaid_0000041
value: 12.0
name: k_a

metaid_0000018
type: Parameter
notes: plasma clearance rate
constant: true
units: metaid_0000041
value: 0.34
name: k10

metaid_0000015
type: Parameter
notes: apparent volume of the central compartment per kg body-weight
constant: true
units: metaid_0000042
value: 0.32
name: V_C

metaid_0000042
type: SBMLUnitsDef
unit: 736559
unit: 736546
name: liter_per_kg

736559
type: SBMLUnit
exponent: -1.0
scale: 0
multipler: 1.0
kind: KILOGRAM

736546
type: SBMLUnit
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE

metaid_0000010
type: Species
is: C07481
is: CHEBI:27732
name: C_p
initial concentration: NaN
has only substance units: false
in compartment: metaid_0000004
is: SBO:0000247
constant: false
initial amount: 0.0
boundary condition: false

metaid_0000023
type: Parameter
notes: first order rate of entry/exit to/from effector site
constant: true
units: metaid_0000041
value: 2.03
name: k_eo