Hepatic elimination kinetics of organic anions in rats: developmental aspects and influence of phenobarbital.
Maturation and phenobarbital inducibility of hepatic uptake of the organic anions indocyanine green (ICG) and eosine were studied in rats of different ages. Bile duct ligation reduced the ICG and eosine liver concentration in young rats. Therefore, bile duct ligation cannot be recommended for uptake investigations in rats of different ages. The longest elimination half life time (12.4 min) was found in 10-day-old rats within the first 15 min after i.v. administration of 38 mumol ICG/kg. In 20-day-old rats the ICG half life was significantly shorter than in adult 110-day-old rats (5.8 versus 9.6 min). Phenobarbital pretreatment did not alter the ICG elimination half lives in 10-, 20- and 110-day-old rats. The shortest elimination half life time of eosine was found in 60-day-old rats (33.0 min versus 80.3 min in 10-day-old rats and 62.4 min in 240-day-old ones). Phenobarbital pretreatment did not influence eosine serum concentrations. Our results indicate for ICG that uptake comes to maturity earlier than biliary excretion. Differences between ICG and eosine in maturation of the two transport steps support the assumption of more than one carrier for exogenous organic anions. Dye uptake was not altered after phenobarbital and, consequently, cannot be responsible for enhanced biliary dye excretion in differently aged rats.
D000375:Aging; D000818:Animals; D000838:Anions / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D004801:Eosine Yellowish-(YS); D006207:Half-Life; D007208:Indocyanine Green; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000838:Anions; D007208:Indocyanine Green; D004801:Eosine Yellowish-(YS); D010634:Phenobarbital