title: Biliary excretion of temocapril in zone 1- and zone 3-injured rat.
abstract: 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.
authors.affiliation: Department of Medicine, Teikyo University School of Medicine, Itabashi, 173-8605, Tokyo, Japan
authors.forename: H
authors.initials: H
authors.lastname: Takikawa
authors.forename: N
authors.initials: N
authors.lastname: Sano
authors.forename: T
authors.initials: T
authors.lastname: Onishi
authors.forename: M
authors.initials: M
authors.lastname: Ohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Nishikawa