Linked Life Data

2958611

Source:http://linkedlifedata.com/resource/pubmed/id/2958611

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1987-11-13
pubmed:abstractText
Children with Down syndrome and acute lymphocytic leukemia (ALL) have poor tolerance to antineoplastic drugs, including methotrexate (MTX). We evaluated MTX pharmacokinetics and toxicity in five patients with Down syndrome and ALL who had received multiple high doses of MTX (1 g/m2). Three control patients without Down syndrome were matched to each case according to sex, race, age, and initial leukocyte count. Median MTX plasma concentrations, measured 42 hours after infusion, were significantly higher in patients with Down syndrome versus control patients (average 0.47 vs 0.24 mumol/L, respectively, P = 0.03). When a 42-hour MTX concentration of 0.5 mumol/L was used to identify patients at risk for toxicity, more courses were considered at high risk for toxicity among patients with Down syndrome (31 of 62, 50%) than in control patients (13 of 214, 6.1%, P less than 0.0001). The average MTX clearance was 64.1 mL/min/m2 in Down syndrome vs an average control value of 80.6 mL/min/m2 (P = 0.13). Toxicity after each high-dose MTX course was graded according to standardized criteria. Grades 2 through 4 gastrointestinal toxicity and grades 3 and 4 hematologic toxicity occurred more frequently in the patients with Down syndrome (36% and 13.4% of courses, respectively) vs the control patients (3.6% and 0.9% respectively, P less than 0.0001 for both). This higher frequency of toxicity occurred despite higher doses and prolonged duration of leucovorin given to all patients with Down syndrome. We conclude that altered MTX pharmacokinetics may contribute to the higher incidence of MTX-induced toxicity seen in patients with Down syndrome.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3476
pubmed:author
pubmed:issnType
Print
pubmed:volume
111
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
606-12
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Pharmacokinetics and toxicity of methotrexate in children with Down syndrome and acute lymphocytic leukemia.
pubmed:affiliation
Pharmaceutical Division, St. Jude Children's Research Hospital, Memphis, TN 38101.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't