Biliary excretion of temocapril in zone 1-and zone 3-injured rat

Temocapril is a prodrug of an angiotensin-converting enzyme inhibitor, temo caprilat, a substrate of multidrug resistance protein 2. Hepatocytes in zon e 1 play a role in the uptake and biliary excretion of bile acids under phy siological condition, and those in zone 3 may play a role only with their h igh-dose load. To investigate the pharmacokinetics of temocapril in liver i njury, biliary excretion of temocapril was studied in zone 1- and zone 3-in jured rats, caused by allyl alcohol and bromobenzene, respectively. Biliary excretion of a tracer dose of radiolabeled temocapril was delayed both in zone 1 and the zone 3 injury, but the extent of inhibition was more promine nt in zone 3 injury. Since biliary excretion of organic anions was decrease d only in zone 1 injury in our previous study, the present findings indicat e that decreased biliary excretion of temocaprilat in zone 3 injury is caus ed by the inhibition of the metabolism from temocapril to temocaprilat. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.