Experimental methods for studying drug uptake in the head and brain.
A number of techniques have been developed to study the disposition of drugs in the head and, in particular, the role of the blood-brain barrier (BBB) in drug uptake. The techniques can be divided into three groups: in-vitro, in-vivo and in-situ. The most suitable method depends on the purpose(s) and requirements of the particular study being conducted. In-vitro techniques involve the isolation of cerebral endothelial cells so that direct investigations of these cells can be carried out. The most recent preparations are able to maintain structural and functional characteristics of the BBB by simultaneously culturing endothelial cells with astrocytic cells. The main advantages of the in-vitro methods are the elimination of anaesthetics and surgery. In-vivo methods consist of a diverse range of techniques and include the traditional Brain Uptake Index and indicator diffusion methods, as well as microdialysis and positron emission tomography. In-vivo methods maintain the cells and vasculature of an organ in their normal physiological states and anatomical position within the animal. However, the shortcomings include renal and hepatic elimination of solutes as well as the inability to control blood flow. In-situ techniques, including the perfused head, are more technically demanding. However, these models have the ability to vary the composition and flow rate of the artificial perfusate. This review is intended as a guide for selecting the most appropriate method for studying drug uptake in the brain.
Foster
K A
KA
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Australia. kfoster@medicine.pa.uq.edu.au
Roberts
M S
MS
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D006257:Head / Q000502:physiology*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004364:Pharmaceutical Preparations