Interactions of Cationic Drugs and Cardiac Glycosides at the Hepatic Uptake Level: Studies in the Rat in Vivo, Isolated Perfused Rat Liver, Isolated Rat Hepatocytes and Oocytes Expressing oatp2

다국어 초록 (Multilingual Abstract)

(Received May 9, 2002)
This paper deals with a crucial mechanism for interaction of basic drugs and cardiac glycosides
at the hepatic uptake level. Available literature data is provided and new material is presented
to picture the differential transport inhibition of bulky (type2) cationic drugs by a number
of cardiac glycosides in rat liver. It is shown that the so called organic anion transporting peptide
2 (oatp2) is the likely interaction site: differential inhibition patterns as observed in oocytes
expressing oatp2, could be clearly identified also in isolated rat hepatocytes, isolated perfused
rat liver and the rat in vivo. The anticipation of transport interactions at the hepatic clearance
level should be based on data on the relative affinities of interacting substrates for the transport
systems involved along with knowledge on the pharmacokinetics of these agents as well
as the chosen dose regimen in the studied species. This review highlights the importance of
multispecific tranporter systems such as OATP, accommodating a broad spectrum of organic
compounds of various charge, implying potential transport interactions that can affect body distribution
and organ clearance.