DDMODEL00000298: Executable_sultiame_nonlinear_PK

  public model
Short description:
The model describes the PK of sultiame after administration of three single oral doses of 50, 100 and 200 mg in open-label at four to six weeks interval in 4 healthy volunteers. Serial measurements in plasma, erythrocytes and urines were performed. The plasma maximal concentrations (Cmax) showed striking non-linear disposition of sultiame, with a ten-fold increase while doses were doubled. Conversely, whole blood Cmax increased less than dose-proportionally whilst staying much higher than in plasma. A three-compartment model incorporating a saturable ligand to receptor binding was devised. The model was expressed in terms of differential equations and first-order rate constants of absorption (ka), elimination (ke), association to (kon) and dissociation from (koff) receptors, maximal binding capacity (Btot), apparent central volume of distribution (V2) and erythrocytes’ volume of distribution (V3).
Original code
Kim Dao, Thierry Buclin
Context of model development: Dose & Schedule Selection and Label Recommendation;
Discrepancy between implemented model and original publication: There are no model differences with the publication that is under review;
Long technical model description: Theoretical model and differential equations will be available in Figure 1 of the publication (under submission) ;
Model compliance with original publication: Yes;
Model implementation requiring submitter’s additional knowledge: No;
Modelling context description: Non-linear distribution in erythrocytes;
Modelling task in scope: estimation;
Nature of research: Early clinical development (Phases I and II);
Therapeutic/disease area: CNS;
Annotations are correct.
This model is not certified.
  • Model owner: Kim Dao
  • Submitted: Jun 24, 2019 8:13:44 AM
  • Last Modified: Jul 16, 2019 3:51:31 PM
Revisions
  • Version: 16 public model Download this version
    • Submitted on: Jul 16, 2019 3:51:31 PM
    • Submitted by: Thierry Buclin
    • With comment: Updated model annotations.
  • Version: 15 public model Download this version
    • Submitted on: Jun 25, 2019 8:14:09 AM
    • Submitted by: Kim Dao
    • With comment: Edited model metadata online.
  • Version: 13 public model Download this version
    • Submitted on: Jun 25, 2019 8:11:24 AM
    • Submitted by: Kim Dao
    • With comment: Model revised without commit message
  • Version: 10 public model Download this version
    • Submitted on: Jun 24, 2019 8:13:44 AM
    • Submitted by: Kim Dao
    • With comment: Updated model annotations.
 
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