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Abstract

Stereoselectivity of glutathione conjugation: blood elimination of alpha-bromoisovalerylurea enantiomers and biliary excretion of the conjugates in unanesthetized normal or congenitally jaundiced rats.

M Polhuijs, F Kuipers, R J Vonk and G J Mulder
Journal of Pharmacology and Experimental Therapeutics June 1989, 249 (3) 874-878;
M Polhuijs
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F Kuipers
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R J Vonk
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G J Mulder
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Abstract

Stereoselectivity of glutathione conjugation was studied in unanesthetized normal and congenitally jaundiced rats (Groningen Yellow), using the separate enantiomers of alpha-bromoisovalerylurea (BIU) as substrates. The blood elimination half-lives of (R)- or (S)-BIU were 8 and 38 min, respectively. The excretion half-lives of the GSH conjugates in bile in normal rats showed a similar difference: (R)-BIU yielded exclusively (S)-IU-S-G with a T1/2 of 12 min, and (S)-BIU yielded only (R)-IU-S-G with a T1/2 of 36 min. In normal rats 45-47% of the dose of (R)-BIU and (S)-BIU was found in bile as glutathione (GSH) conjugate, and 19-25% was excreted in urine as mercapturates. Similar values in the mutant rats indicated that BIU elimination by GSH conjugation was unimpaired, but the GSH conjugates were absent from bile. In the urine twice as much mercapturates was found as in normal rats. The GSH content and the activity of the glutathione-S-transferases in the liver were similar in mutant and controls. The data on blood elimination of the BIU enantiomers and biliary excretion of the GSH conjugates suggest that for (S)-BIU the conjugation step is rate-limiting, whereas for (R)-BIU a transport step into bile may be rate-limiting.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 249, Issue 3
1 Jun 1989
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Abstract

Stereoselectivity of glutathione conjugation: blood elimination of alpha-bromoisovalerylurea enantiomers and biliary excretion of the conjugates in unanesthetized normal or congenitally jaundiced rats.

M Polhuijs, F Kuipers, R J Vonk and G J Mulder
Journal of Pharmacology and Experimental Therapeutics June 1, 1989, 249 (3) 874-878;

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Abstract

Stereoselectivity of glutathione conjugation: blood elimination of alpha-bromoisovalerylurea enantiomers and biliary excretion of the conjugates in unanesthetized normal or congenitally jaundiced rats.

M Polhuijs, F Kuipers, R J Vonk and G J Mulder
Journal of Pharmacology and Experimental Therapeutics June 1, 1989, 249 (3) 874-878;
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