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*3-METHYLCHOLANTHRENE
*CHLORDANE
*PHENOBARBITAL
*PHENYLBUTAZONE
Journal of Pharmacology And Experimental Therapeutics, Vol. 168, Issue 2, 218-223, 1969
Copyright © 1969 by American Society for Pharmacology and Experimental Therapeutics

BILIARY FLOW AFTER MICROSOMAL ENZYME INDUCTION

CURTIS D. KLAASSEN 1

1 Clinical Pharmacology and Toxicology Center, Department of Pharmacology, University of Kansas Medical Center, Kansas City, Kansas

Biliary flow and wet liver weight were determined in rats after treatment with various microsomal enzyme inducers for one, two, three, five or seven days. Phenobarbital (PB) was the only agent which produced a significant increase in biliary flow (control vs. treated: 60 vs. 90 µl/min/kg). With chlordane, nikethamide, phenylbutazone and chlorcyclizine treatment, there was a tendency in the direction of an increase in biliary flow (60 vs. approximately 75 µl/min/kg), but the increases were not statistically significant. Biliary flow was not altered in rats pretreated with 3,4-benzpyrene and 3-methylcholanthrene. Significant increases in drug-metabolizing activity were demonstrated by a decrease in zoxazolamine paralysis time with PB, 3-methylcholanthrene, 3 ,4-benzpyrene and chlordane, but only PB significantly enhanced biliary flow. Therefore, microsomal drug-metabolizing enzyme induction itself does not result in an increase in biliary flow. Livers from the PB-and 3-methylcholanthrene-treated rats exhibited the greatest increase in wet weight followed by 3,4-benzpyrene, nikethamide and chlorcyclizine. Therefore, no direct correlation exists between the ability of microsomal enzyme inducers to increase liver weight and to enhance biliary flow. Dosages of 30 to 150 mg/kg of PB, when administered once daily for seven days, resulted in significant increases in biliary flow and liver weight. Rats were also treated with PB (75 mg/kg) for periods of up to three weeks, and the biliary flow and liver weights remained elevated. When rats were treated for seven days with PB, biliary flow and liver weight returned to control levels within a week after the last dose.

Submitted on February 10, 1969
Accepted on April 25, 1969




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