Clinical and pharmacologic study of orally administered uridine.
Effects of oral administrations of uridine were investigated in a study of six healthy volunteer control subjects and nine patients with metastatic colorectal cancer. Oral uridine was studied as single-dose administrations at doses escalating from 0.3 to 12 g/m2 and as multiple-dose administrations every 6 hours for 3 days at doses from 5 to 10 g/m2. The maximum tolerated dose (MTD) was 10 to 12 g/m2 for a single dose of uridine and 5 g/m2 for the multiple-dose regimen. Diarrhea was the dose-limiting toxic effect. Single-dose oral uridine resulted in an increase in plasma uridine concentrations in the range of 60 to 80 microM after doses of 8 to 12 g/m2. At these doses, bioavailability of oral uridine ranged from 5.8% to 9.9%. At the MTD of 5 g/m2 in the multiple-dose uridine schedule, steady-state plasma uridine levels of approximately 50 microM were achieved. Further studies should explore the role of oral uridine in the modulation of the toxicity of fluorouracil.
van Groeningen
C J
CJ
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
Peters
G J
GJ
Nadal
J C
JC
Laurensse
E
E
Pinedo
H M
HM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014529:Uridine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity
D014529:Uridine