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Journal of Pharmacology And Experimental Therapeutics, Vol. 161, Issue 2, 361-366, 1968
Copyright © 1968 by American Society for Pharmacology and Experimental Therapeutics

STUDIES ON THE MECHANISM OF PHENOBARBITAL-ENHANCED SULFOBROMOPHTHALEIN DISAPPEARANCE

Curtis D. Klaassen 1 and Gabriel L. Plaa 1

1 Oakdale Toxicology Center, Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, Iowa

Increased plasma disappearance of sulfobromophthalein (BSP) was demonstrated after rats were treated with phenobarbital (75 mg/kg) once daily for 3 days. Since BSP undergoes storage, metabolism and excretion by the liver, these parameters were examined to determine which process or processes are altered by treatment with phenobarbital. No change in hepatic storage was demonstrated, but significant increases of in vitro metabolism, biliary transport maximum and bile flow were observed. With a dibrominated analog of BSP, phenol-3,6-dibromphthalein disulfonate (DBSP), and indocyanine green, which apparently are not biotransformed before their excretion, an enhanced plasma disappearance was also exhibited after phenobarbital treatment. With DBSP no significant alteration in hepatic storage was demonstrated, but an enhanced biliary transport maximum and bile flow were demonstrated. The data support the view that the enhanced biliary excretion of these dyes is an important factor after phenobarbital treatment and that the role of increased biotransformation is not as important for the enhanced plasma disappearance of these dyes as might be expected from the effect of phenobarbital on the biologic half-life of other substances.

Submitted on November 8, 1967
Accepted on February 12, 1968




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Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics.