MODEL1006230040
type: SBMLModel
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parameter: 288414
parameter: 288410
parameter: 288415
parameter: 288424
parameter: 288411
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parameter: 288403
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modified:
  W3 CDTF: Fri Jun 25 13:44:49 BST 2010
substance units: 178797
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curated: false
is described by: http://identifiers.org/pubmed/16758333
parameter: 288413
parameter: 288406
parameter: 288420
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modified:
  W3 CDTF: Fri Jun 25 13:44:49 BST 2010
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
parameter: 288418
volume units: 290956
parameter: 288419
units def: 397231
modified:
  W3 CDTF: Fri Jun 25 13:44:49 BST 2010
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 …
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creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
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parameter: 288408
units def: 397255
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
created:
  W3 CDTF: Fri Jun 25 13:44:49 BST 2010
parameter: 288421
parameter: 288402
name: Yang2006_Methadone_PKmodel

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value: 6.6685
name: Ca

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value: 2148.0
name: Va

397231
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397243
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value: 6445.65
name: Qc

397147
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288409
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value: 198.0
name: Km

288423
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288400
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288385
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288408
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name: Vmax

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288402
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name: B