RT Journal Article
SR Electronic
T1 The influence of dehydrocholate on hepatic uptake and biliary excretion of 3H-taurocholate and 3H-ouabain.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1
OP 7
VO 4
IS 1
A1 D K Meijer
A1 R J Vonk
A1 E J Scholtens
A1 W G Levine
YR 1976
UL http://dmd.aspetjournals.org/content/4/1/1.abstract
AB The hepatic uptake and biliary excretion of 3H-taurocholate and 3H-ouabain was studied in the rat during saline (control) and dehydrocholate infusions. Dehydrocholate (140 mumol/hr) did not influence the plasma disappearance nor the biliary excretion of taurocholate after a single iv injection (37 mumol/kg). Bile production in the dehydrocholate experiment was increased 2- to 3-fold compared with controls. The biliary transport maximum for exogenously administered taurocholate was determined by constant infusion to be 135.0 +/- 3.0 mumol/hr (22 mumol/min/g of liver). Concomitant infusions of 140 mumol of dehydrocholate per hr did not alter the maximal taurocholate output. The effects of the two bile salts on bile flow were additive. Dehydrocholate (140 mumol/hr) reduced the biliary excretion of 3H-ouabain (0.8 mumol/kg) and elevated the secondary slow component of the plasma disappearance of the cardiac glycoside. The hepatic levels of ouabain were increased compared with controls. It is concluded that dehydrocholate interferes with ouabain transport at the canalicular level but not with primary hepatic uptake. Taurocholate (140 mumol/hr) failed to influence the total biliary output of ouabain. These differences and the lack of interaction between dehydrocholate and taurocholate suggest a hepatic transporting pathway for taurocholate which differs from that for taurocholate which differs from that for dehydrocholate and/or its metabolites.