EFFECTS OF PHENOBARBITAL ON THE PLASMA DISAPPEARANCE AND BILIARY EXCRETION OF DRUGS IN RATS

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

The effects of phenobarbital (PB) pretreatment on the plasma disappearance and biliary excretion of sulfobromophthalein, bilirubin, phenol red, probenecid, phenol-3,6-dibromphthalein disulfonate, amaranth, succinylsulfathioazole, chlorothiazide, taurocholic acid, indocyanine green (ICG), ouabain and procaine amide ethyl bromide were investigated. A significant enhancement in the plasma disappearance of a number of agents was observed after PB treatment. Since an enhanced plasma disappearance and biliary excretion of phenol-3,6-dibromphthalein distilfonate, amaranth and ouabain were observed (agents which are not conjugated before their excretion), it appears that increased conjugation is not necessary for PB treatment to exert this effect. With ICG, an enhanced plasma disappearance was observed in the PB-treated rats, but no increase in excretion was detected, suggesting an increased hepatic storage of ICG after PB treatment. Except for ICG, all the drugs which disappeared from the plasma at a faster rate after PB treatment also were excreted into the bile at a faster rate. This enhanced plasma disappearance and biliary excretion after PB treatment is not limited only to organic acids, for similar effects were demonstrated with an organic base, procaine amide ethyl bromide, and an organic neutral compound, ouabain. The enhanced biliary excretion after PB appears to correlate with the increase in biliary flow produced by PB. However, the increase in biliary flow does not have a similar effect on all compounds, because little or no increase in the plasma disappearance or biliary excretion of phenol red and succinyl sulfathiazole are observed after PB treatment. In conclusion, it appears that the increase in biliary flow and excretion produced by PB treatment in rats plays an important role in the enhanced plasma disappearance of a number of drugs that are excreted into the bile.

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