PHARMACOKINETICS OF 5-FLUOROURACIL ADMINISTERED ORALLY, BY RAPID INTRAVENOUS AND BY SLOW INFUSION

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (7) , 2223-2228
Abstract
Pharmacokinetic studies of 5-fluorouracil (5-FUra) were performed on 18 patients divided into the following 3 groups: 7 patients were given 5-FUra i.v. by rapid injection; 5 patients received the drug p.o.; 6 patients were treated by continuous i.v. infusion for 96 h. Rapid i.v. injection was manifested by high early levels of drug in plasma and bone marrow, with a rapid fall afterwards. Administration of 5-FUra p.o. gave rise to erratic plasma values due to greater variability in absorption; 96 h i.v. infusions showed constant levels of the drug in plasma and significantly (50- to 1000-fold) less 5-FUra in bone marrow. The main difference observed between rapid injection and slow infusion in the kinetics of the drug was the very high level of 5-FUra reached by rapid injection in plasma and bone marrow, which was of short duration (min) when compared to the low sustained levels observed during infusion. This route-dependent pharmacokinetic profile is consistent with the reported absence of myelosuppression in prolonged infusion and may be related to the resultant lower levels of 5-FUra achieved in bone marrow.