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Cancer Treat Rep. 1986 Jul;70(7):903-4.

Plasma pharmacokinetics of 5-FU given by continuous infusion with allopurinol.


We determined the steady-state plasma levels of 5-FU when the drug was administered by continuous infusion for 5 days during 21 courses in patients with metastatic colorectal carcinoma receiving concomitant oral allopurinol given at a dose of 300 mg orally three times/day. The steady-state plasma level increased from 3.37 to 7.49 microM with dose increases from 1.25 to 2.25 g/m2/day. Clearance ranged from 1.79 to 2.41 L/min/m2. Although we observed a large day-to-day variation and a large patient-to-patient variation in plasma 5-FU levels at any given dose level, these were not significant. The plasma level of 5-FU increased linearly with dose. The difference between 5-FU plasma levels with dose was significant (P = 0.002). When the levels were adjusted for patient-to-patient and day-to-day variation the difference remained significant (P = 0.02). The results indicate that: (a) plasma levels of 5-FU may show large but insignificant variation from patient to patient and from day to day; and (b) steady-state plasma levels and 5-FU increased linearly with dose.

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