D-optimal designs for parameter estimation for indirect pharmacodynamic response models.

This report generates efficient experimental designs (dose, sampling times) for parameter estimation for four basic physiologic indirect pharmacodynamic response (IDR) models. The principles underlying IDR models and their response patterns have been well described. Each IDR model explicitly contains four parameters, k (in) (production), k (out) (loss), I (max)/S (max) (capacity) and IC (50)/SC (50) (sensitivity).

Optimal design for estimating parameters of the 4-parameter hill model.

Many drug concentration-effect relationships are described by nonlinear sigmoid models. The 4-parameter Hill model, which belongs to this class, is commonly used. An experimental design is essential to accurately estimate the parameters of the model.