Constraint-based perturbation analysis with cluster Newton method: a case study of personalized parameter estimations with irinotecan whole-body physiologically based pharmacokinetic model.

ABSTRACT: BACKGROUND:Drug development considering individual varieties among patients becomes crucial to improve clinical development success rates and save healthcare costs. As a useful tool to predict individual phenomena and correlations among drug characteristics and individual varieties, recently, whole-body physiologically based pharmacokinetic (WB- PBPK) models are getting more attention. WB-PBPK models generally have a lot of drug-related parameters that need to be estimated, and the estimations are difficult because the observed data are limited. Furthermore, parameter estimation in WB-PBPK models may cause overfitting when applying to individual clinical data such as urine/feces drug excretion for each patient in which Cluster Newton Method (CNM) is applicable for parameter estimation. In

SUBMITTER: Asami S 

PROVIDER: S-EPMC5763286 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature