In vivo super(19)F NMR spectroscopy of the antimetabolite 5-fluorouracil and its analogues. An assessment of drug metabolism

In vivo super(19)F NMR spectroscopy of the antimetabolite 5-fluorouracil and its analogues. An assessment of drug metabolism

The metabolism of 5-fluorouracil (5FU) and its analogues 2'-deoxy-5-fluorouridine (2'FdURD), 5'-deoxy-5-fluorouridine (5'FdURD) and R,S-1-(tetrahydro-2-furyl)-5-fluorouracil (Ftorafur) has been studied by super(19)F NMR in rat liver and the rat S.G. Prolactinoma. In experiments u...

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Veröffentlicht in:Biochemical pharmacology 1990-01, Vol.39 (5), p.857-863
Hauptverfasser: Prior, MJW, Maxwell, R J, Griffiths, J R
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creator Prior, MJW
Maxwell, R J
Griffiths, J R
description The metabolism of 5-fluorouracil (5FU) and its analogues 2'-deoxy-5-fluorouridine (2'FdURD), 5'-deoxy-5-fluorouridine (5'FdURD) and R,S-1-(tetrahydro-2-furyl)-5-fluorouracil (Ftorafur) has been studied by super(19)F NMR in rat liver and the rat S.G. Prolactinoma. In experiments using i.v. bolus injections of 0.46 mmol/kg 5FU was cleared more rapidly from the liver than 5'FdURD (t sub(1/2) of 4.7 plus or minus 0.6 vs 15.8 plus or minus 0.8 min, P < 0.001). Alphafluoro-beta-alanine (FBALA) production was almost identical after 5FU or 2'FdURD but slower and more sustained after 5'FdURD and still slower after Ftorafur. Both 5FU and 2'FdURD caused formation of toxic fluoronucleotides in S.G. Prolactinomas when administered i.v (0.92 mmol/kg bolus).
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title In vivo super(19)F NMR spectroscopy of the antimetabolite 5-fluorouracil and its analogues. An assessment of drug metabolism
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