Sampling Strategies for Population Analysis: a Theoretical Study to Support Practical Results Obtained with Caffeine in Premature Neonates
A.C. Falcao(1,2) , M.M. Fernandez de Gatta, A. Dominguez-Gil, J.M. Lanao
Department of Pharmacy and Pharmaceutical Technology, University of Salamanca, Salamanca, Spain, Lab. of Pharmacology(1) , Faculty of Pharmacy, University of Coimbra, Portugal , Supported(2) by Junta Nacional de Investigacao Cientifica e Tecnologia (JNICT), Portugal
Population pharmacokinetic analysis is a commonly used tool to analyse routine clinical data. In recent years some work has been done using simulations to evaluate and compare experimental design for sparse data experiments. However, the simulations studies usually began from theory to practice and shows us the better way to obtain good final parameter estimates (fixed and random effects).
In the present study, based on our own results for caffeine in premature neonates (1), we attempted through a simulation study to explain some problems that we had during the model- building process, specially the absence of inter-individual parameter estimate for Vd.
The simulations data sets included two samples from 50 subjects and were generated with a total randomized scheme. A lot of combinations of sampling times with any intra and inter-posological intervals possibilities were examined in order to obtain the answers for our questions. For each simulation 30 replications were carried out by using the NONMEM program and an adequate study about the precision and bias for the different parameters were made.
From a qualitative point of view the principal conclusions are:
- the necessity of concentrations obtained after the loading dose;
- the dispersion of concentrations inter-posological intervals;
- the presence of Cmax. independently of the posological interval considered.
The quantitative results (tables and graphics) will be presented later due the limited space allowed for abstracts.
Moreover, this conclusions could be extrapolated for other drugs with the same kinetic profile of caffeine in premature infants (half-life about 80 hours).
(1) A.C. Falcao et al. -Caffeine pharmacokinetics in a pediatric population. Second meeting of PAGE. Greenford/London/U.K.; June 1994