Drug enterohepatic circulation and disposition: constituents of systems pharmacokinetics

Abstract

Drug disposition information constitutes a part of systems pharmacokinetics, and becomes imperative when a drug shows significant effects at its disproportionally low blood concentration. The situation could result from outweighing the parent drug in tissues over in blood and/or from its active metabolites. Fractions of certain drugs absorbed from the intestine to the systemic circulation via the portal vein can return to the intestine via the bile duct and the sphincter of Oddi - a complementary nonrenal elimination route termed the enterohepatic circulation (EHC). Here, we critically evaluate the existing methods, techniques and animal models used for determining drug distribution, elimination and EHC, and collectively portray characteristics of 43 drugs that undergo EHC. EHC could represent an unexplored way to excrete unwanted substrates out of the body. The interdisciplinary analysis galvanizes our efforts to overcome technical gaps in drug discovery and development.