TY - JOUR T1 - STIMULATION OF THE DEVELOPMENT OF THE HEPATIC EXCRETORY MECHANISM FOR OUABAIN IN NEWBORN RATS WITH MICROSOMAL ENZYME INDUCERS JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 212 LP - 218 VL - 191 IS - 2 AU - Curtis D. Klaassen Y1 - 1974/11/01 UR - http://jpet.aspetjournals.org/content/191/2/212.abstract N2 - The LD5O of ouabain in a 3-day-old rat is about 1/40 that in the adult. This difference is due largely to the inability of the liver to remove ouabain from the plasma and to excrete it into bile. New born rats were treated with microsomal enzyme inducers to determine whether they would enhance the development of the hepatic excretory system and thus decrease the toxicity of ouabain. 1-, 6-, 11-, 16-, 21-, 26- or 31-day-old rats were pretreated for 4 days with phenobarbital (PB, 33 and 50 mg/kg), pregnenolone-l6α-carbonitrile (PCN, 75 mg/kg), spironolactone (S, 75 mg/kg) or 3-methylcholanthrene (20 mg/kg). On the 5th day, Ouabain was administered (4 mg/kg i.v.). Fifteen minutes later the amount of ouabain in the plasma and the liver and the amount excreted into the intestine were determined. PB, PCN and S enhanced the hepatic clearance of ouabain in the neonates, but 3-methylcholanthrene did not. PCN and S were more effective than PB. In the 10-day-old rats, 3 to 4 times more ouabain was in the liver and bile of the PCN and S rats than in control rats. When 15 mg/kg of ouabain were administered (i.p.) to 10-day-old rats, 92% died within 24 hours after 3-methylcholanthrene pretreatment, 90% died. However, the rats were protected when they were pretreated with other inducers: after PCN none died, after S 33% died and after PB 68% died. In summary, some microsomal enzyme inducers will markedly enhance the development of the hepatic excretory mechanisms that remove ouabain from the plasma thus decreasing its toxicity. © 1974 by The Williams & Wilkins Co. ER -