156998
constant: false
value: NaN
name: tprime
type: Parameter

156933
constant: true
size: 1.0
spatial dimensions: 3.0
type: Compartment

157014
constant: true
value: 8.0
name: pEf3
type: Parameter

157043
constant: true
value: 0.368
name: mena total delay (fast)
type: Parameter

157007
constant: true
value: 3.0
name: AMT_dose
type: Parameter

157010
constant: true
value: 0.2
name: pEs1
type: Parameter

157047
constant: false
value: NaN
name: X3
type: Parameter

BIOMD0000000238
parameter: 157031
is described by: http://identifiers.org/pubmed/17009101
parameter: 157027
parameter: 156997
parameter: 157007
parameter: 157009
parameter: 156943
rule: 156949
parameter: 157015
parameter: 156985
parameter: 157001
name: Overgaard2007_PDmodel_IL21
notes: This a model from the article: PKPD model of interleukin-21 effects on thermoregulation in monkeys--application and evaluation of stochastic differential equations. Overgaard RV, Holford N, Rytved KA, Madsen H. Pharm Res. 2007 Feb;24(2):298-309. PUBMED , Abstract: PURPOSE: To describe the pharmacodynamic effects of recombinant human interleukin-21 (IL-21) on core body temperature in cynomolgus monkeys using basic mechanisms of heat regulation. A major effort was devoted to compare the use of ordinary differential equations (ODEs) with stochastic differential equations (SDEs) in pharmacokinetic pharmacodynamic (PKPD) modelling. METHODS: A temperature model was formulated including circadian rhythm, metabolism, heat loss, and a thermoregulatory set-point. This model was formulated as a mixed-effects model based on SDEs using NONMEM. RESULTS: The effects of IL-21 were on the set-point and the circadian rhythm of metabolism. The model was able to describe a complex set of IL-21 induced phenomena, including 1) disappearance of the circadian rhythm, 2) no effect after first dose, and 3) high variability after second dose. SDEs provided a more realistic description with improved simulation properties, and further changed the model into one that could not be falsified by the autocorrelation function. CONCLUSIONS: The IL-21 induced effects on thermoregulation in cynomolgus monkeys are explained by a biologically plausible model. The quality of the model was improved by the use of SDEs. This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team. For more information see the terms of use . To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellula…
rule: 156970
rule: 156962
parameter: 157030
parameter: 156994
parameter: 157034
is: MODEL0911110000
rule: 156974
parameter: 157029
parameter: 157042
parameter: 157022
parameter: 157038
parameter: 157041
rule: 156957
parameter: 157017
is version of: GO:0060086
parameter: 157045
parameter: 157011
rule: 156969
rule: 156956
is version of: GO:0001659
parameter: 156939
parameter: 156940
length unit: length
rule: 156951
substance units: metaid_0000028
rule: 156960
parameter: 157026
parameter: 157006
rule: 156972
rule: 156977
curated: true
parameter: 157033
compartment: 156933
parameter: 157049
rule: 156964
parameter: 156999
parameter: 157014
parameter: 157021
parameter: 157037
rule: 156976
parameter: 156987
parameter: 156989
parameter: 156993
parameter: 157003
occurs in: http://identifiers.org/taxonomy/9541
parameter: 157050
is version of: http://identifiers.org/omim/605384
rule: 156980
type: SBMLModel
rule: 156958
area units: metaid_0000005
rule: 156961
parameter: 157010
parameter: 157039
parameter: 157019
rule: 156953
parameter: 157047
parameter: 157025
parameter: 156995
volume units: metaid_0000004
parameter: 156941
parameter: 156936
time units: metaid_0000029
rule: 156965
parameter: 157013
parameter: 156998
rule: 156952

157018
constant: false
value: NaN
name: T_day
type: Parameter

157003
constant: false
value: NaN
name: heat conductance
type: Parameter

157033
constant: false
value: NaN
name: gNsTs2
type: Parameter

156943
constant: false
value: NaN
name: Priming
type: Parameter

156994
constant: false
value: NaN
name: circadian rhythm
type: Parameter

157038
constant: false
value: NaN
name: gNfTf3
type: Parameter

157023
constant: false
value: NaN
name: M_day
type: Parameter

156997
constant: true
value: 6.73
name: t_night
type: Parameter

157015
constant: true
value: 50.0
name: pEs3
type: Parameter

157006
constant: true
value: 5.35
name: kR
type: Parameter

157042
constant: true
value: 2.45
name: mean total delay (slow)
type: Parameter

157011
constant: true
value: 3.57
name: pEf2
type: Parameter

156939
constant: false
value: 0.0
name: Bound Receptor
type: Parameter

157039
constant: true
value: 4.0
name: No. of transit compartment (slow)
type: Parameter

157046
constant: false
value: NaN
name: X2
type: Parameter

157025
constant: false
value: NaN
name: M_night
type: Parameter

156987
constant: true
value: 1.57
name: temperature difference
type: Parameter

156940
constant: false
value: NaN
name: Slow Effect
type: Parameter

156990
constant: true
value: 24.0
name: tdose1
type: Parameter

157019
constant: false
value: NaN
name: T_night
type: Parameter

157002
constant: true
value: 3.47
name: specific heat constant
type: Parameter

156993
constant: true
value: 120.0
name: tdose3
type: Parameter

157049
constant: false
value: NaN
name: Kf
type: Parameter

157022
constant: true
value: 3.0
name: M_b
type: Parameter

157029
constant: true
value: 1.0
name: delta_high_dose
type: Parameter

156986
constant: true
value: 38.0
name: basiline temperature
type: Parameter

157045
constant: false
value: NaN
name: X1
type: Parameter

156991
constant: true
value: 72.0
name: tdose2
type: Parameter

157041
constant: true
value: 4.0
name: No. of transit compartment (fast)
type: Parameter

157026
constant: true
value: 45.12
name: t_prime
type: Parameter

157035
constant: false
value: NaN
name: gNfTf1
type: Parameter

156941
constant: false
value: NaN
name: Fast Effect
type: Parameter

157001
constant: true
value: 1.1375
name: rate constant Metabolism
type: Parameter

157009
constant: true
value: 1.0
name: pEf1
type: Parameter

157021
constant: false
value: NaN
name: heat conductance baselinevalue
type: Parameter

157031
constant: false
value: NaN
name: gNsTs1
type: Parameter

157005
constant: true
value: 0.144
name: pEtot
type: Parameter

156936
constant: false
value: 3.5
name: Metabolic rate
type: Parameter

157013
constant: true
value: 2.43
name: pEs2
type: Parameter

156999
constant: true
value: 86400.0
name: day_length
type: Parameter

156985
constant: true
value: 21.0
name: ambient temperature
type: Parameter

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

157027
constant: true
value: 0.2229166
name: alpha
type: Parameter

156995
constant: true
value: 17.5
name: t_day
type: Parameter

156937
constant: false
value: 38.785
name: Temperature
type: Parameter

157030
constant: false
value: NaN
name: M_night_baseline
type: Parameter

157037
constant: false
value: NaN
name: gNfTf2
type: Parameter

156989
constant: true
value: 0.0258
name: kinc
type: Parameter

157034
constant: false
value: NaN
name: gNsTs3
type: Parameter

157017
constant: false
value: NaN
name: f2_drug
type: Parameter

157050
constant: false
value: NaN
name: Ks
type: Parameter

W3 CDTF: Thu Feb 11 13:35:13 GMT 2010

ORG:
  orgname: University of Auckland
n:
  given: Catherine
  family: Lloyd

W3 CDTF: Thu Nov 12 14:29:18 GMT 2009

orgname: Novo Nordisk A/S, Copenhagen, Denmark.

n:
  given: Rune Viig
  family: Overgaard