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Journal of Pharmacology and Experimental Therapeutics

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Abstract

Multiple systems for the biliary excretion of organic anions in rats: liquiritigenin conjugates as model compounds.

H Shimamura, H Suzuki, M Hanano, A Suzuki, O Tagaya, T Horie and Y Sugiyama
Journal of Pharmacology and Experimental Therapeutics October 1994, 271 (1) 370-378;
H Shimamura
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H Suzuki
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M Hanano
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A Suzuki
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O Tagaya
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T Horie
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Y Sugiyama
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Abstract

Liquiritigenin (LG), 2, 3-dihydro-7-hydroxy-2-(4-hydroxyphenyl)-(S)-4H-1-benzopyran-4-1, is metabolized to five kinds of conjugates (glucuronides and sulfates) that are excreted predominantly into the bile (Shimamura et al., 1993). Using LG as a model compound, we studied the multiplicity for the biliary excretion of conjugates in vivo. LG was administered i.v. as a bolus to Sprague-Dawley rats (SD rats) that received i.v. infusions of the inhibitors [glycyrrhizin (GR), dibromosulfophthalein (DBSP) and indocyanine green (ICG)] at their maximal transport rates. The infusion of GR and that of DBSP reduced significantly the biliary excretion of all the conjugates except LG 4',7-O-disulfate (M3), whereas infusion of ICG did not affect the excretion of conjugates. To minimize the effect of the other tissues on the disposition of the conjugates, the apparent biliary excretion clearance (CLbile,app) was calculated. The CLbile,app values of LG 4'-O-glucuronide (M1), LG 7-O-glucuronide (M2), LG 4'-O-glucuronide 7-O-sulfate (M4) and LG 7-O-glucuronide 4'-O-sulfate (M5) were significantly reduced by GR and DBSP infusion, whereas the CLbile, app value of M3 was not affected by these inhibitors. The CLbile, app values of all the conjugates except M2 were not reduced by ICG infusion. In Eisai hyperbilirubinemic rats, which have a hereditary defect in the canalicular transport system for several organic anions, the biliary excretion clearance of M1, M2, M4 and M5 was markedly reduced, whereas that of M3 was comparable with that in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 271, Issue 1
1 Oct 1994
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Abstract

Multiple systems for the biliary excretion of organic anions in rats: liquiritigenin conjugates as model compounds.

H Shimamura, H Suzuki, M Hanano, A Suzuki, O Tagaya, T Horie and Y Sugiyama
Journal of Pharmacology and Experimental Therapeutics October 1, 1994, 271 (1) 370-378;

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Abstract

Multiple systems for the biliary excretion of organic anions in rats: liquiritigenin conjugates as model compounds.

H Shimamura, H Suzuki, M Hanano, A Suzuki, O Tagaya, T Horie and Y Sugiyama
Journal of Pharmacology and Experimental Therapeutics October 1, 1994, 271 (1) 370-378;
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