Method to evaluate the systemic exposure in toxicological and pharmacological studies

摘要

A method of estimating the average exposure within a population of subjects to a pharmacological substance, administered according to a given protocol, by estimating the area under the concentration curve (AUC), characterised in that the area under the population concentration curve is estimated by the steps of obtaining measurements of the drug concentrations in each of the subjects at any time during the study, independently from the time when measurements of the drug concentration level in the other subjects are being taken; building a hierarchical stochastic model composed of the population and of the individual levels; determining the posterior probability distribution of the average AUC from the sample data and hence the average population AUC. The exposure of an individual and its precision within the sample of individuals can be determined by determining the posterior probability distribution of the individual AUC from the sample data. The posterior probability model may be obtained by using a Markov Chain Monte Carlo algorithm, such as Gibbs Sampling.