Drug interactions in biotransformation of 1-phthalidyl 5-fluorouracil to 5-fluorouracil in rat liver.

Two rat liver hydrolases were found to be involved in the metabolism of 1-phthalidyl 5-fluorouracil (PH-FU) to 5-fluorouracil (5-FU), one of which was induced by phenobarbital (PB) treatment of rats. Both inducible and constitutive enzyme were soluble and showed different characteristics in gel filtration and response to inhibitors. Further study showed that the blood level of PH-FU could be modulated by PB-pretreatment or coadministration of enzyme inhibitors to rats.