NDLI: Semiparametric mixed-effects analysis of PK/PD models using differential equations

Content Provider	Springer Nature Link
Author	Wang, Yi Eskridge, Kent M. Zhang, Shunpu
Copyright Year	2008
Abstract	Motivated by the use of semiparametric nonlinear mixed-effects modeling on longitudinal data, we develop a new semiparametric modeling approach to address potential structural model misspecification for population pharmacokinetic/pharmacodynamic (PK/PD) analysis. Specifically, we use a set of ordinary differential equations (ODEs) with form dx/dt = A(t)x + B(t) where B(t) is a nonparametric function that is estimated using penalized splines. The inclusion of a nonparametric function in the ODEs makes identification of structural model misspecification feasible by quantifying the model uncertainty and provides flexibility for accommodating possible structural model deficiencies. The resulting model will be implemented in a nonlinear mixed-effects modeling setup for population analysis. We illustrate the method with an application to cefamandole data and evaluate its performance through simulations.
Starting Page	443
Ending Page	463
Page Count	21
File Format	PDF
ISSN	1567567X
Journal	Journal of Pharmacokinetics and Pharmacodynamics
Volume Number	35
Issue Number	4
e-ISSN	15738744
Language	English
Publisher	Springer US
Publisher Date	2008-09-10
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Compartmental models Splines Mixed-effects modeling Biochemistry Biomedical Engineering Veterinary Medicine Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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