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397339
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288416
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units: 397231
value: 3431.0
name: Vv
type: Parameter

397111
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multipler: 60.0
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397219
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scale: 0
multipler: 60.0
kind: SECOND
type: SBMLUnit

288403
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units: 397255
value: 0.48
name: F
type: Parameter

397267
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kind: MOLE
type: SBMLUnit

MODEL1006230040
rule: 288389
created:
  W3 CDTF: Fri Jun 25 13:44:49 BST 2010
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
modified:
  W3 CDTF: Fri Jun 25 13:44:49 BST 2010
parameter: 288414
parameter: 288410
parameter: 288415
parameter: 288424
parameter: 288411
rule: 288393
modified:
  W3 CDTF: Fri Jun 25 13:44:49 BST 2010
parameter: 288409
rule: 288397
parameter: 288423
parameter: 288404
parameter: 288400
parameter: 288403
area units: 291053
units def: 397123
time units: 397351
units def: 397183
length unit: 076409
modified:
  W3 CDTF: Fri Jun 25 13:44:49 BST 2010
substance units: 178797
units def: 397147
parameter: 288416
rule: 288392
curated: false
is described by: http://identifiers.org/pubmed/16758333
parameter: 288413
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
parameter: 288406
parameter: 288420
rule: 288395
units def: 397327
parameter: 288405
units def: 397099
parameter: 288418
type: SBMLModel
volume units: 290956
parameter: 288419
units def: 397231
notes: This a model from the article: Population-based analysis of methadone distribution and metabolism using an age-dependent physiologically based pharmacokinetic model. Yang F, Tong X, McCarver DG, Hines RN, Beard DA. J Pharmacokinet Pharmacodyn 2006 Aug;33(4):485-518 16758333 , 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 enzyme expression levels and plasma orosomucoid (ORM2) concentrations, a Monte-Carlo-based simulation of methadone kinetics in a pediatric population was performed. The simulation predicts extreme variability in plasma concentrations and clearance kinetics for methadone in the pediatric population, based on standard dosing protocols. In addition, it is shown that when doses are designed for individuals based on prior protein expression information, inter-individual variability in methadone kinetics may be greatly reduced. This …
units def: 397291
rule: 288391
units def: 397351
rule: 288394
compartment: 288385
parameter: 288408
units def: 397255
parameter: 288421
parameter: 288402
name: Yang2006_Methadone_PKmodel
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd

397243
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multipler: 1.0
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397303
exponent: -1.0
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kind: MOLE
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397159
exponent: 1.0
scale: -3
multipler: 1.0
kind: LITRE
type: SBMLUnit

288413
constant: true
units: dimensionless
value: 5.0
name: age
type: Parameter

288406
constant: false
units: 397183
value: NaN
name: R
type: Parameter

288402
constant: false
units: 397255
value: NaN
name: B
type: Parameter

397363
exponent: 1.0
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multipler: 60.0
kind: SECOND
type: SBMLUnit

397327
unit: 397339
name: first_order_rate_constant
type: SBMLUnitsDef

397135
exponent: 1.0
scale: 0
multipler: 3.1536E7
kind: SECOND
type: SBMLUnit

397291
unit: 397315
unit: 397303
name: per_micromolar
type: SBMLUnitsDef

288423
constant: true
units: dimensionless
value: 15.61
name: P
type: Parameter

397099
unit: 397111
name: minute
type: SBMLUnitsDef

288418
constant: false
units: 397255
value: NaN
name: Cv
type: Parameter

397195
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

288414
constant: false
units: 397255
value: 6.6685
name: Ca
type: Parameter

397279
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

288410
constant: false
units: dimensionless
value: NaN
name: fu
type: Parameter

288409
constant: true
units: 397255
value: 198.0
name: Km
type: Parameter

288420
constant: true
units: 397231
value: 1454.0
name: V
type: Parameter

288424
constant: true
units: 397147
value: 6445.65
name: Qc
type: Parameter

397255
unit: 397279
unit: 397267
name: micromolar
type: SBMLUnitsDef

397171
exponent: -1.0
scale: 0
multipler: 60.0
kind: SECOND
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397207
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

288405
constant: true
units: 397291
value: 0.8532
name: K2
type: Parameter

288415
constant: true
units: 397231
value: 2148.0
name: Va
type: Parameter

397147
unit: 397171
unit: 397159
name: flow
type: SBMLUnitsDef

397231
unit: 397243
name: ml
type: SBMLUnitsDef

288400
constant: true
units: 397099
value: NaN
name: time
type: Parameter

288419
constant: false
units: 397255
value: 0.0
name: C
type: Parameter

397351
unit: 397363
name: time
type: SBMLUnitsDef

288385
constant: true
units: litre
size: 1.0
spatial dimensions: 3.0
type: Compartment

397315
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

288408
constant: true
units: 397183
value: 0.009433
name: Vmax
type: Parameter

397123
unit: 397135
name: year
type: SBMLUnitsDef

288411
constant: false
units: dimensionless
value: NaN
name: ISF
type: Parameter

288421
constant: true
units: 397147
value: 1221.34
name: Q
type: Parameter

288404
constant: true
units: dimensionless
value: 1.0
name: n2
type: Parameter