Fundamentals in Population Pharmacokinetics: Mathematics in Linear Mixed Effects Model and Nonlinear Mixed Effects Model

Nonlinear Mixed Effects Model for Swine Growth

Growth curves are often fit to serial live weight data typically every 14-21 days from 50 lbs. to 250 lbs. live weight. This serial data usually has underlying relationships or correlations amongst the serial live weight observations. Heavier pigs at birth and weaning usually have a competitive advantage and remain heavier than the remaining pigs of the group. Also, the variation amongst the pi...

Model Building for Nonlinear Mixed-Effects Models

Nonlinear mixed-effects models involve both fixed effects and random effects. Model building for nonlinear mixed-effects models is the process of determining the characteristics of both the fixed and the random effects so as to give an adequate but parsimonious model. We describe procedures based on information criterion statistics for comparing different structures of the random effects compon...

Nonlinear mixed effects model analysis of the pharmacokinetics of metoprolol in routinely treated Japanese patients.

This study was performed to estimate the mean pharmacokinetic parameters of routinely administered metoprolol in middle-aged and elderly Japanese patients. Whole blood concentration data (65 samples) at steady-state following repetitive administration to 34 patients were analyzed using a nonlinear mixed effects model. A one-compartment model was parameterized in terms of oral clearance (CL/F) a...

Covariate Model Building in Nonlinear Mixed Effects Models

Smooth random effects distribution in a linear mixed model.

A linear mixed model with a smooth random effects density is proposed. A similar approach to P-spline smoothing of Eilers and Marx (1996, Statistical Science 11, 89-121) is applied to yield a more flexible estimate of the random effects density. Our approach differs from theirs in that the B-spline basis functions are replaced by approximating Gaussian densities. Fitting the model involves maxi...