Related Experiment Video
Updated: Jul 8, 2026

Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
Published on: July 23, 2016
Prediction of shrinkage of individual parameters using the bayesian information matrix in non-linear mixed effect
François Pierre Combes1, Sylvie Retout, Nicolas Frey
1University Paris Diderot, Sorbonne Paris Cité INSERM, UMR 738, 16, rue Henri Huchard, F-75018, Paris, France. francois.combes@inserm.fr
Purpose:
When information is sparse, individual parameters derived from a non-linear mixed effects model analysis can shrink to the mean. The objective of this work was to predict individual parameter shrinkage from the Bayesian information matrix (M BF ). We 1) Propose and evaluate an approximation of M BF by First-Order linearization (FO), 2) Explore by simulations the relationship between shrinkage and precision of estimates and 3) Evaluate prediction of shrinkage and individual parameter precision.
Methods:
We approximated M BF using FO. From the shrinkage formula in linear mixed effects models, we derived the predicted shrinkage from M BF . Shrinkage values were generated for parameters of two pharmacokinetic models by varying the structure and the magnitude of the random effect and residual error models as well as the design. We then evaluated the approximation of M BF FO and compared it to Monte-Carlo (MC) simulations. We finally compared expected and observed shrinkage as well as the predicted and estimated Standard Errors (SE) of individual parameters.
Results:
M BF FO was similar to M BF MC. Predicted and observed shrinkages were close . Predicted and estimated SE were similar.
Conclusions:
M BF FO enables prediction of shrinkage and SE of individual parameters. It can be used for design optimization.
Related Concept Videos
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
Noncompartmental Analysis: Miscellaneous Pharmacokinetic Parameters
One key aspect of the noncompartmental approach is determining a drug's total clearance. This can be done by dividing the drug dose by the area under the concentration-time curve from zero to infinity. The area under the concentration-time curve represents the drug's...
Shrinkage in Concrete
When concrete is still in its plastic state, it can undergo a decrease in volume by about 1% of its absolute volume. This decrease is known as plastic shrinkage. It arises either...
Drying Shrinkage
A portion of this drying shrinkage can be reversed; if the concrete is...
Carbonation Shrinkage
The concrete's permeability is slightly reduced as calcium carbonate produced during the reaction fills its pores. Furthermore, its strength is slightly enhanced as the water released during the reaction...
Dosage Regimens: Partial Pharmacokinetic Parameters

