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Clin Pharmacokinet. 1978 Jul-Aug;3(4):330-6.

Fluorouracil therapy in patients with carcinoma of the large bowel: a pharmacokinetic comparison of various rates and routes of administration.

Abstract

The pharmacokinetics of fluorouracil after oral, intravenous and rectal administration were compared in 12 patients with colorectal cancers. Oral administration of 10 to 15 mg/kg gave variable plasma levels (0 to 10.5 microgram/ml) and bioavailability (0 to 74%; mean 28%). Bioavailability increased markedly with increases in dose, suggesting saturation of the 'first pass' hepatic metabolism of the drug. Differences in bioavailability could not be related to standard liver function tests or the presence of metastatic deposits in the liver. Plasma levels were not detectable after rectal administration in the 4 patients studied and were very low (0 to 8 microgram/ml) during high dose (20 to 30 mg/kg/24h) slow intravenous infusion in 6 patients. These findings indicate that different dose schedules and routes of administration produce markedly different plasma levels. They suggest that the rate of degradation of fluorouracil by the liver is quite variable and may become saturated with increasing dose. For these reasons monitoring of plasma levels of the drug in individual patients may be useful.

PMID:
678346
[PubMed - indexed for MEDLINE]
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