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

• Published in: Hepatology research Vol. 20; no. 2; p. 216
• Main Authors: Takikawa, H, Sano, N, Onishi, T, Ohashi, M, Hasegawa, Y, Nishikawa, K
• Format: Journal Article
• Language: English
• Published: Netherlands 01.06.2001
• ISSN: 1386-6346
• DOI: 10.1016/s1386-6346(00)00132-7

Temocapril is a prodrug of an angiotensin-converting enzyme inhibitor, temocaprilat, a substrate of multidrug resistance protein 2. Hepatocytes in zone 1 play a role in the uptake and biliary excretion of bile acids under physiological condition, and those in zone 3 may play a role only with their high-dose load. To investigate the pharmacokinetics of temocapril in liver injury, biliary excretion of temocapril was studied in zone 1- and zone 3-injured 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 prominent in zone 3 injury. Since biliary excretion of organic anions was decreased only in zone 1 injury in our previous study, the present findings indicate that decreased biliary excretion of temocaprilat in zone 3 injury is caused by the inhibition of the metabolism from temocapril to temocaprilat.