Landberg2009 - Alkylresorcinol Dose Response

  public model
Model Identifier
BIOMD0000000948
Short description
Pharmacokinetic model of alkylresorcinols. Both plasma AR concentrations and urinary metabolites in 24-h samples showed a dose-response relation to increased AR intake, which strongly supports the hypothesis that ARs and their metabolites may be useful as biomarkers of whole-grain wheat and rye intakes.
Format
SBML (L2V4)
Related Publication
  • Dose response of whole-grain biomarkers: alkylresorcinols in human plasma and their metabolites in urine in relation to intake.
  • Landberg R, Aman P, Friberg LE, Vessby B, Adlercreutz H, Kamal-Eldin A
  • The American journal of clinical nutrition , 1/ 2009 , Volume 89 , Issue 1 , pages: 290-296 , PubMed ID: 19056600
  • Department of Food Science, Swedish University of Agriculture Science, Uppsala, Sweden. rikard.landberg@lmv.slu.se
  • Alkylresorcinols (ARs), phenolic lipids almost exclusively present in the outer parts of wheat and rye grains in commonly consumed foods, have been proposed as specific dietary biomarkers of whole-grain wheat and rye intakes.The objective was to assess the dose response of plasma ARs and the excretion of 2 recently discovered AR metabolites in 24-h urine samples in relation to AR intake and to establish a pharmacokinetic model for predicting plasma AR concentration.Sixteen subjects were given rye bran flakes containing 11, 22, or 44 mg total ARs 3 times daily during week-long intervention periods separated by 1-wk washout periods in a nonblinded randomized crossover design. Blood samples were collected at baseline, after the 1-wk run-in period, and after each treatment and washout period. Two 24-h urine samples were collected at baseline and after each treatment period.Plasma AR concentrations and daily excretion of 2 urinary AR metabolites increased with increasing AR dose (P < 0.001). Recovery of urinary metabolites in 24-h samples decreased with increasing doses from approximately 90% to approximately 45% in the range tested. A one-compartment model with 2 absorption compartments with different lag times and absorption rate constants adequately predicted plasma AR concentrations at the end of each intervention period.Both plasma AR concentrations and urinary metabolites in 24-h samples showed a dose-response relation to increased AR intake, which strongly supports the hypothesis that ARs and their metabolites may be useful as biomarkers of whole-grain wheat and rye intakes.
Contributors
Submitter of the first revision: Matthew Roberts
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Matthew Roberts, Krishna Kumar Tiwari

Metadata information

isDescribedBy (1 statement)
PubMed 19056600

hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

hasPart (2 statements)
KEGG Compound Resorcinol
ChEBI 5-alkylresorcinol

is (3 statements)
Experimental Factor Ontology dose response design
BioModels Database MODEL1803050001
BioModels Database BIOMD0000000948

Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags

Connected external resources

SBGN view in Newt Editor

Name Description Size Actions

Model files
Landberg2009.xml SBML L2V4 representation of Landberg2009 - Alkylresorcinol Dose Response 29.03 KB Preview | Download

Additional files
Landberg2009.cps COPASI file 48.53 KB Preview | Download
Landberg2009.sedml SEDML file for the model 1.70 KB Preview | Download
figure2.jpg Attempt at reproducing figure 3. 14.95 KB Preview | Download

  • Model originally submitted by : Matthew Roberts
  • Submitted: May 21, 2018 3:31:34 PM
  • Last Modified: May 12, 2020 5:35:25 AM
Revisions
  • Version: 5 public model Download this version
    • Submitted on: May 12, 2020 5:35:25 AM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Automatically added model identifier BIOMD0000000948
  • Version: 3 public model Download this version
    • Submitted on: May 21, 2018 3:31:34 PM
    • Submitted by: Matthew Roberts
    • With comment: Uploaded COPASI and curated figure to facilitate the curation process in the future.

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
F2 0.0 nmol
AR Dose

5-alkylresorcinol ; Resorcinol 		485.0 nmol
AR A1

Resorcinol ; 5-alkylresorcinol 		0.0 nmol
F1 0.0 nmol
AR A2

5-alkylresorcinol ; Resorcinol 		0.0 nmol
AR Central

Resorcinol ; 5-alkylresorcinol 		0.01 nmol
Reactions
Reactions Rate Parameters
F2 = piecewise(0, time < Lag_time_2, 0.048) [] Lag_time_2 = 4.7
AR_Dose => AR_A2; F2 F2*AR_Dose []
AR_Dose => AR_A1; F1 F1*AR_Dose []
AR_A1 => AR_Central k_a_1*AR_A1 k_a_1 = 0.3
F1 = piecewise(0, time < Lag_time_1, piecewise(0.1, (time >= Lag_time_1) && (time < Lag_time_2), 0.052)) [] Lag_time_1 = 0.9; Lag_time_2 = 4.7
AR_A2 => AR_Central k_a_2*AR_A2 k_a_2 = 1.8
Curator's comment:
(added: 12 May 2020, 05:35:10, updated: 12 May 2020, 05:35:10)
Figure 3 results are reproduced here. Model encoded and annotated using COPASI. Plotting done using MATLAB.