Linked Life Data

3986795

Source:http://linkedlifedata.com/resource/pubmed/id/3986795

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1985-6-19
pubmed:abstractText
In vitro studies of certain lymphoid tumor cells show potentiation of 1-beta-D-arabinofuranosylcytosine (ara-C) effects by uridine because it elevates intracellular uridine triphosphate, resulting in increased ara-C triphosphate levels. Seven-day continuous i.v. infusions of uridine at 123 mg/kg/h (2.5 g/sq m/h) were studied in 5 male beagles. Steady state levels of uridine were reached within 4 to 6 h and ranged from 2 to 5 X 10(-4) M over the course of the infusion. Steady state uracil levels ranged from 4 to 10 X 10(-4) M. After the end of infusion, uridine and uracil levels fell with a half-life of approximately 15 and 18 min, respectively. Toxicity in 2 dogs treated at this dose was limited to minimal diarrhea and a transient rise of alkaline phosphatase to 2 to 3 times normal. No drug toxicity was evident at sacrifice on Days 7 or 72. Three dogs received a 7-day infusion of ara-C plus uridine followed approximately 4 weeks later by an infusion of ara-C alone (or the same drugs in the reverse sequence). Coinfusion of 2.5 or 5.0 mg/kg/day (50 or 100 mg/sq m/day) of ara-C had no significant effects on uridine plasma levels or postinfusion half-lives. Similarly, no consistent effect was seen of uridine on ara-C plasma levels. Uridine coinfusion with ara-C resulted in a definite potentiation of myelosuppression; at 5.0 mg/kg/day X 7 of ara-C white blood cell and platelet nadirs (X 10(3)/microliters) were 0.8 and 15 as compared to 3.6 and 66, respectively, with ara-C alone. One-third of the dogs developed reversibly elevated transaminases with the combination treatment. The results show that a minimally toxic dose of uridine enhances bone marrow and probably hepatic toxicity of coadministered ara-C.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2572-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
Pharmacology and toxicology of a seven-day infusion of 1-beta-D-arabinofuranosylcytosine plus uridine in dogs.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't