Analytical expressions for combining population pharmacokinetic parameters from different studies.
We provide a set of formulas that allow the combination of separately performed analyses of population pharmacokinetic (PK) studies, without any further computational effort. More specifically, given the point estimates and uncertainties of two population PK analyses, the formulas provide the point estimates and uncertainties of the combined analysis, including the mean population values, the between-subject variability, and the residual variability. To derive the formulas we considered distributional assumptions applicable for the conjugate priors of the Bayesian problem of "unknown mean and variance." In order to demonstrate the approach, the formulas were applied to an example involving the results of fitting two real experimental datasets. The formulas presented offer an easy-to-use method of combining different analyses particularly applicable to a combination of literature information.
Dokoumetzidis
Aristides
A
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK. dokoumetzidis@manchester.ac.uk
Aarons
Leon
L
D000818:Animals; D003627:Data Interpretation, Statistical; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D011153:Population; D051381:Rats