Interspecies Comparison of Distribution of Cyclosporin A in the Central Compartment

David Mendl, Milan Lázníček (laznicek@faf.cuni.cz)

Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic

Summary

Interactions of cyclosporin A with components of the central distribution compartment (plasma proteins and blood cells) were determined in four animal species, namely man, bovine, rabbit and rat. It was demonstrated that cyclosporin A is very strongly bound to plasma proteins (98 — 99 %) and also to blood cells in their suspension (92 — 97 %) in all species. In interspecies comparison, significant differences in distribution of the cyclosporin A in the whole blood were determined. While about three quarters of amount of cyclosporin A were distributed to blood cells and one quarter of the drug was bound to plasma proteins in man, that for rabbit was nearly inverse. Ultrafiltration method by using Centrex UF-0.5 Filters 10 KMWCO (Schleicher and Schuel) gave comparable results of plasma protein binding in comparison with equlibrium dialysis. Advantage of ultrafiltration against the standard method of equilibrium dialysis is above all determination speed (6 minutes vs. 4 hours).