Microdialysis in pharmacokinetics

Abstract

Microdialysis is a method by which the extracellular fluid from almost any organ or fluid compartment can be sampled without loss of volume for long periods of time. By this method direct access is gained to previously intractable fluid spaces such as the brain extracellular fluid and the mechanisms of transfer over, for example, the blood brain barrier (BBB) and the blood placenta barrier can be studied with fewer assumptions made than previously. We here concentrate on three aspects of the use of microdialysis in pharmacokinetics. Firstly, some of the practical experimental requirements are reviewed with particular attention paid to the recovery problem. Secondly, the calculation of pharmacokinetic parameter estimates is discussed including an algorithm for dealing with multicompartment models and direct studies of transfer rate constants. Thirdly, the possibility to model and experimentally examine various transport mechanisms is discussed. The theoretical results are applied to data from a study of the anti-HIV drugs zidovudine and alovudine (3'-fluorothymidine) and their distribution across the blood brain barrier in rats.