PT  - JOURNAL ARTICLE
AU  - Klaassen, Curtis D.
TI  - EFFECT OF MICROSOMAL ENZYME INDUCERS ON THE BILIARY EXCRETION OF CARDIAC GLYCOSIDES
DP  - 1974 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 201--211
VI  - 191
IP  - 2
4099  - http://jpet.aspetjournals.org/content/191/2/201.short
4100  - http://jpet.aspetjournals.org/content/191/2/201.full
SO  - J Pharmacol Exp Ther1974 Nov 01; 191
AB  - Digitoxin (2.5 mg/kg), digoxin (7 mg/kg) or ouabain (5 mg/kg) was given i.v. to rats pretreated for 4 days with phenobarbital (PB, 50 mg/kg), pregnenolone-16α-carbonitrile (PCN, 75 mg/kg), spironolactone (S, 75 mg/kg) or 3-methylcholanthrene (3-MC, 20 mg/kg). Plasma disappearance and biliary excretion of the cardiac glycosides were measured for 2 hours. PCN and S increased the rate of biliary excretion of radioactivity associated with digitoxin by 1000 and 400% respectively. PB-treatment increased the excretion by only 25% and 3-MC decreased it. Similarly with 3H-digoxin, PCN and S increased the rate of biliary excretion of tritium by 400 and 150%, respectively, whereas PB increased it by 25% and 3-MC decreased it. The excretion of radioactivity as polar metabolites in the rats given 3H-digoxin was not increased as has been reported for digitoxin. The increased excretion was due to a more lipid-soluble metabolite, digoxin-bisdigitoxoside, and to the parent compound. PCN, S and PB increased the biliary excretion of ouabain, a cardiac glcoside that is not biotransformed before its excretion, by 150, 50 and 80%, respectively. These studies demonstrate that there is a marked difference in the ability of microsomal enzyme inducers to enhance the biliary excretion of cardiac glycosides and that the mechanism is not solely dependent on biotransformation of the glycoside to more polar metabolites. © 1974 by The Williams & Wilkins Co.