期刊
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
卷 4, 期 11, 页码 641-649出版社
WILEY
DOI: 10.1002/psp4.12040
关键词
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资金
- National Institutes of Health [R01 CA138264, F32 CA154213]
- UNCF-Merck Science Initiative
- European Research Council [341117]
- European Research Council (ERC) [341117] Funding Source: European Research Council (ERC)
Mathematical models can support the drug development process by predicting the pharmacokinetic (PK) properties of the drug and optimal dosing regimens. We have developed a pharmacokinetic model that includes a biochemical molecular interaction network linked to a whole-body compartment model. We applied the model to study the PK of the anti-vascular endothelial growth factor (VEGF) cancer therapeutic agent, aflibercept. Clinical data is used to infer model parameters using a Bayesian approach, enabling a quantitative estimation of the contributions of specific transport processes and molecular interactions of the drug that cannot be examined in other PK modeling, and insight into the mechanisms of aflibercept's antiangiogenic action. Additionally, we predict the plasma and tissue concentrations of unbound and VEGFbound aflibercept. Thus, we present a computational framework that can serve as a valuable tool for drug development efforts.
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