Linked Life Data

1699279

Source:http://linkedlifedata.com/resource/pubmed/id/1699279

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5 Suppl 8
pubmed:dateCreated
1990-11-19
pubmed:abstractText
Fludara I.V. (fludarabine phosphate) (2-F-ara-adenosine monophosphate [2-F-ara-AMP], NSC 312887) is the 5'-phosphate of 2-F-ara-A-(9-beta-D-arabinofuranosyl-2-fluoroadenine), a derivative of ara-A that is resistant to deamination and selectively inhibits DNA synthesis. Concurrent with the phase I evaluation of 2-F-ara-AMP administered as a single intravenous (IV) bolus every 21 days to patients with advanced malignancy, plasma pharmacokinetic profiles of 2-F-ara-A were determined in 30 patients following the rapid infusion (2 to 5 minutes) of doses of 2-F-ara-AMP ranging from 80 to 260 mg/m2. The parent drug was almost quantitatively converted to 2-F-ara-A by apparent first-pass metabolism, with maximum levels of 2-F-ara-A and very low levels (less than 1 fmol/L) of 2-F-ara-AMP observed only in the plasma samples obtained shortly after dosing (2 to 4 minutes). The plasma concentration-time profiles exhibited three exponential phases. Plasma concentrations were computer fitted to a three-compartment open model using a zero-order input function for the injection period. The 2-F-ara-A harmonic mean half-lives were t1/2 alpha = 4.97 minutes, t1/2 beta = 1.38 hours, t1/2 gamma = 10.41 hours, and the mean residence time was 10.51 hours. The rate-limiting process for elimination of the drug from the body appeared to be release from tissue binding sites. The mean total-body plasma clearance was 67.98 +/- 19.58 mL/min/m2 (mean +/- SD). The mean central compartment volume of distribution (V1) was 7.49 L/m2 or 0.20 L/kg. The mean steady-state volume of distribution (Vdss) was 44.17 L/m2 or 1.19 L/kg, indicating that 2-F-ara-A is distributed and bound to the tissues of the body. Total-body clearance and the volume parameters Vdss and Vd gamma decreased with an increase in serum creatinine, indicating that these pharmacokinetic parameters depend upon renal function. Dose reduction in patients with renal dysfunction is recommended.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0093-7754
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18-32
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Pharmacokinetics of 2-F-ara-A (9-beta-D-arabinofuranosyl-2-fluoroadenine) in cancer patients during the phase I clinical investigation of fludarabine phosphate.
pubmed:affiliation
Ohio State University Comprehensive Cancer Center, Columbus.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.