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Xenobiotica
the fate of foreign compounds in biological systems
Volume 17, 1987 - Issue 6
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Original Article

Metabolism of 1-phthalidyl 5-fluorouracil in rat liver and enzyme induction by phenobarbital

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Pages 759-768 | Received 05 Jun 1986, Published online: 30 Sep 2009
 

Abstract

1. When 1-phthalidyl 5-fluorouracil (PH-FU) was incubated with isolated rat hepatocytes, 5-fluorouracil, 2-carboxybenzaldehyde (CBA) and α-hydroxymethylbenzoic acid (HMB) were detected as the major metabolites.

2. The enzymes involved in the metabolism of PH-FU, PH-FU hydrolase and CBA reductase are cytosolic and were induced by treating the rats with phenobarbital (PB). Treatment of rats with 3-methylcholanthrene (3-MC) did not affect either enzyme activity.

3. The PB-induced PH-FU hydrolase was inhibited by NADH and several aldehydes, while NAD stimulated the hydrolase and protected it from inactivation by SH reagents.

4. Study in vivo revealed that treatment of rats with PB accelerated the metabolism of PH-FU in the liver and markedly decreased the blood PH-FU after its oral administration to rats, which resulted in reduction of the anti-tumour activity of PH-FU. This activity was not affected by treatment of the rats with 3-MC.

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