Hepatic extraction of nonmetabolizable xenobiotics in rats
Iga, T.; Klaassen, C.D.
Journal of Pharmacology and Experimental Therapeutics 211(3): 690-697
1979
ISSN/ISBN: 0022-3565 PMID: 512932 Document Number: 145161
The apparent hepatic extraction of nonmetabolized xenobiotics, whch which are often used to measure the hepatic excretory function in experimental laboratory animal, was determined by comparison of the area under the plasma concentration time curve after administration of various doses into the femoral and portal vein of rats. The cardiac glycoside, ouabain and 4 organic anions, phenol 3,6-dibromophthalein disulfonate, amaranth, indocyanine green and rose bengal were studied. The apparent hepatic extraction of ouabain was .apprx. 50%, but it decreased as the dose increased. A marked dose-dependent decrease of apparent hepatic extraction was revealed for phenol 3,6-dibromophthalein and amaranth. The marked differences in the area under the plasma concentration time curve observed after intraportal and systemic administration was not always reflected by a difference in their excretion into the bile, suggesting that the first-pass effect of these excretion into the bile, suggesting that the first-pass effect of these nonbiotransformable substances is due to their transport from the plasma into the liver rather than liver into bile. The apparent hepatic extraction indocyanine green and rose bengal were surprisingly low at doses above 1 mg/kg, and no significant difference in the area under the plasma concentration time curve was shown between femoral and portal vein administration. Since these compounds have a low hepatic extraction at doses used to measure hepatic function in rats, changes in hepatic blood flow would not markedly alter their clearance; if a decrease in clearance is observed after hepatic injury, the reason would most likely be due to a decrease in the intrinsic ability of the liver to extract the compounds rather than a change in blood flow.