Population pharmacokinetic model of sibrotuzumab, a humanized monoclonal antibody directed against fibroblast activation protein. The model was built from 1844 serum concentrations after multiple i.v. infusions in 60 advanced or metastatic carcinoma patients in three Phase I and II clinical studies.
|Context of model development:||Variability sources in PK and PD (CYP, Renal, Biomarkers);|
|Discrepancy between implemented model and original publication:||Contary to the original publication, inter-occasion variability on bioavailability was not implemented.;|
|Long technical model description:||Two-compartment PK model with combined linear and saturable elimination. Inter-individual variability on linear and nonlinear clearance and volumes of distribution. Inter-occasion variability on bioavailability after repeated IV dosing (also accounts for uncertainty in actual dose level). Body weight is used as a covariate on linear and nonlinear clearance and volumes of distribution.;|
|Model compliance with original publication:||No;|
|Model implementation requiring submitter’s additional knowledge:||No;|
|Modelling context description:||To understand PK and variability in cancer patients of a new monoclonal antibody;|
|Modelling task in scope:||simulation;|
|Nature of research:||Early clinical development (Phases I and II);|
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- Model owner: Niklas Hartung
- Submitted: Jul 15, 2016 10:24:49 AM
- Last Modified: Jul 15, 2016 10:24:49 AM
Independent variable T
Structural Model sm
Continuous / Residual Data
Estimation Step estimStep_1
Initial estimates for non-fixed parameters
1) Estimate the population parameters