Document Detail


Variability of 6-mercaptopurine pharmacokinetics during oral maintenance therapy of children with acute leukemia.
MedLine Citation:
PMID:  2615529     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of some environmental and genetic factors on the inter- and intraindividual variations of 6-mercaptopurine (6-MP) pharmacokinetics were studied in children on oral remission maintenance therapy for acute lymphoblastic leukemia or non-Hodgkin's lymphoma. Blood samples were obtained 0-4 h after drug intake. 6-MP concentrations were determined in plasma and in erythrocyte concentrates. The influence of food on the pharmacokinetics was examined in a prospective study of 15 children. Each child was examined four times, twice in the fasted state and twice after intake of a standardized, milky, breakfast. There were pronounced inter- and intraindividual variations. Food intake seemed to reduce these variations but there were no significant changes in peak concentrations and area under the plasma concentration vs time curves (AUC) between the fasted and fed states. Food intake reduced the time to peak concentration both in plasma, from 1.8 h to 1.1 h (P less than 0.01) and in red blood cells, from 1.8 h to 1.3 h (P less than 0.01). Retrospective subdivision of the patients indicated a tendency for different pharmacokinetic patterns according to dose; five out of seven patients receiving greater than 70 mg m-2 had a higher AUC in the fasting state, while five out of eight patients receiving less than 70 mg m-2 had a higher AUC in the fed state. The cytochrome P-450-dependent hydroxylation capacity was evaluated with debrisoquine but no correlation was found to the pharmacokinetics of 6-MP.
Authors:
P Lafolie; O Björk; S Hayder; L Ahström; C Peterson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Medical oncology and tumor pharmacotherapy     Volume:  6     ISSN:  0736-0118     ISO Abbreviation:  Med Oncol Tumor Pharmacother     Publication Date:  1989  
Date Detail:
Created Date:  1990-03-07     Completed Date:  1990-03-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8405039     Medline TA:  Med Oncol Tumor Pharmacother     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  259-65     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
6-Mercaptopurine / administration & dosage,  blood,  pharmacokinetics*
Administration, Oral
Adolescent
Child
Child, Preschool
Debrisoquin / blood
Erythrocytes / metabolism
Fasting
Female
Humans
Lymphoma, Non-Hodgkin / blood,  drug therapy*
Male
Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood,  drug therapy*
Chemical
Reg. No./Substance:
1131-64-2/Debrisoquin; 50-44-2/6-Mercaptopurine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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