Archives of Pharmacal Research

, Volume 25, Issue 4, pp 397–415 | Cite as

Interactions of cationic drugs and cardiac glycosides at the hepatic uptake level: studies in the ratin vivo, isolated perfused rat liver, isolated rat hepatocytes and oocytes expressing oatp2

Research Articles Reviews


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 ratin 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.

Key words

Organic cations Cardiac glycosides Basic drugs Hepatic Uptake oatp2 Drug interactions Oubain K-Strophanthoside Digitoxin Rocuronium Curare-like agents 


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Copyright information

© The Pharmaceutical Society of Korea 2002

Authors and Affiliations

  • Dirk K. F. Meijer
    • 1
  • Jessica E. van Montfoort
    • 1
  1. 1.Department of Pharmacokinetics and Drug DeliveryGroningen University Institute of Drug Exploration (GUIDE)GroningenThe Netherlands

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