Does the metabolite uracil arabinoside inhibit cytosine arabinoside (Ara-C) penetration into the cerebrospinal fluid during high-dose Ara-C therapy?
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 mumol/l 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 mumol/l. After repetitive doses on d 2-6 the drug concentrations increased from about 3 mumol/l just before infusion to about 8 mumol/l 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.
van Prooijen
H C
HC
Muus
P
P
Roelofs
J M
JM
Punt
K
K
D000328:Adult; D001086:Arabinofuranosyluracil / Q000097:blood / Q000134:cerebrospinal fluid*; D001692:Biological Transport; D001812:Blood-Brain Barrier; D003561:Cytarabine / Q000037:antagonists & inhibitors* / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D014529:Uridine / Q000031:analogs & derivatives*
D003561:Cytarabine; D001086:Arabinofuranosyluracil; D014529:Uridine