Linked Life Data

11129502

Source:http://linkedlifedata.com/resource/pubmed/id/11129502

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-12-20
pubmed:abstractText
The effects of repeated treatment cycles and different doses on intraindividual variation in oral bioavailability of chlorambucil and its first, active, and more toxic metabolite, phenylacetic acid mustard, were studied. Chlorambucil and phenylacetic acid mustard concentrations were measured with HPLC on Day 1 and on Day 4 in 15 timed blood samples from 11 chronic lymphocytic leukaemia patients receiving chlorambucil therapy cycles. Bioavailability was evaluated also after the first chlorambucil doses of six consecutive treatment cycles repeated every 4 weeks with increasing chlorambucil doses starting with 0.8 mg/kg/4 days, and increased by 0.1 mg/kg/4 days cycle. Area under the concentration-time-curve (AUC) from t=0 to infinite was in average 3.2 hr* microg/ml for the first cycle, and decreased by 17% in four days (P<0.05). The mean distribution half-life of chlorambucil was 0.49 hr and the terminal elimination half-life 2.45 hr. The bioavailability of chlorambucil decreased further when 4-day treatment cycles were repeated. For the fifth cycle, dose-corrected AUC for the first 2 hr was 33% smaller than that for the first cycle (P for trend <0.01). Data suggest accelerated metabolism and elimination of chlorambucil and phenylacetic acid mustard, but reduced oral bioavailability of chlorambucil cannot be excluded. However, except for AUC, none of the pharmacokinetic parameters of chlorambucil changed significantly during the first 4-day treatment period. The maximal plasma concentration and AUC of phenylacetic acid mustard did not change significantly during repeated treatment cycles. According to this trial a dose adjustment of chlorambucil is not necessary during a short-term course, but may be necessary when treatment cycles are repeated. An average increase in the chlorambucil dose of 10% per cycle maintains similar plasma concentration of chlorambucil.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0901-9928
pubmed:author
pubmed:issnType
Print
pubmed:volume
87
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
223-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11129502-Administration, Oral, pubmed-meshheading:11129502-Aged, pubmed-meshheading:11129502-Animals, pubmed-meshheading:11129502-Antimetabolites, Antineoplastic, pubmed-meshheading:11129502-Antineoplastic Agents, Alkylating, pubmed-meshheading:11129502-Area Under Curve, pubmed-meshheading:11129502-Biological Availability, pubmed-meshheading:11129502-Chlorambucil, pubmed-meshheading:11129502-Chromatography, High Pressure Liquid, pubmed-meshheading:11129502-Dose-Response Relationship, Drug, pubmed-meshheading:11129502-Drug Administration Schedule, pubmed-meshheading:11129502-Female, pubmed-meshheading:11129502-Humans, pubmed-meshheading:11129502-Leukemia, Lymphocytic, Chronic, B-Cell, pubmed-meshheading:11129502-Male, pubmed-meshheading:11129502-Middle Aged, pubmed-meshheading:11129502-Phenylacetates
pubmed:year
2000
pubmed:articleTitle
Pharmacokinetics of chlorambucil in patients with chronic lymphocytic leukaemia: comparison of different days, cycles and doses.
pubmed:affiliation
Department of Clinical Chemistry, Tampere University Hospital and University of Tampere Medical School, Finland.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't