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Does the metabolite uracil arabinoside inhibit cytosine arabinoside (Ara‐C) penetration into the cerebrospinal fluid during high‐dose Ara‐C therapy?
Author(s) -
Prooijen Hendrik C.,
Muus Petra,
Roelofs Jan M. M.,
Punt Kees
Publication year - 1986
Publication title -
scandinavian journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0036-553X
DOI - 10.1111/j.1600-0609.1986.tb02664.x
Subject(s) - metabolite , cytosine , cytarabine , uracil , cerebrospinal fluid , pharmacology , chemistry , blood–brain barrier , medicine , leukemia , biochemistry , central nervous system , dna
A patient with acute leukaemia was treated with i.v. 2‐h infusions of Ara‐C at a dose of 3.0 g/m2 every 12 h. During 6 d of therapy the concentrations of the metabolite Ara‐U in the CSF reached rather high levels of between 60 and 70 u.mol/1 from d 2–6 due to high levels of Ara‐U in the plasma. The concentration of Ara‐C in the CSF after the first infusion was 10.8 u.mol/1. After repetitive doses on d 2–6 the drug concentrations increased from about 3 nmol/1 just before infusion to about 8 umol/1 at the end of infusion, indicating inhibition of Ara‐C influx into the CSF during prolonged treatment. We suggest that the high levels of Ara‐U in the plasma interfere with Ara‐C transport across the blood‐brain barrier.