[6-mercaptopurine levels and study of blood lymphocyte subsets during azathioprine treatment of Crohn's disease].
OBJECTIVE
Our aim was to study the relationships between clinical efficacy of azathioprine, 6-mercaptopurine pharmacokinetics and changes in peripheral blood lymphocyte subpopulations induced by azathioprine treatment in Crohn's disease.


METHODS
Twenty-three patients were prospectively followed up for 1 year. Peripheral blood counts, total lymphocytes, CD3+, CD4+, CD8+, CD25+, CD16+CD56+, CD57+ and CD19+ lymphocyte subpopulations were carried out, using flow cytometry, during azathioprine treatment. Pharmacokinetic studies were performed at day 8 and month 3 by measuring 6-mercaptopurine plasma concentration after an oral dose of azathioprine (2 mg/kg). Results were compared in responders (no activity and no steroids) and non-responders.


RESULTS
The decrease in peripheral blood leukocytes and neutrophils was significant after 1 month, reaching 49% and 48% of the pre-treatment values at 1 year; the one of lymphocytes was significant after 6 months and reached 41% at 1 year. Percentages of CD3+, CD4+, CD8+, CD57+, CD16+CD56+ and CD19+ lymphocytes remained unchanged whereas percentage of CD25+ lymphocytes increased from 10% to 28% (P < 0.01). There was a high inter and intraindividual variability of 6-mercaptopurine peak plasma concentration and area under the curve. No significant difference was found between responders (n = 14) and non responders (n = 7) for pharmacokinetic parameters and lymphocyte subpopulations; there was no correlation between lymphocyte subpopulation changes and 6-mercaptopurine pharmacokinetics.


CONCLUSIONS
Monitoring of 6-mercaptopurine plasma concentration and blood lymphocyte subpopulations is of little value in Crohn's disease patients treated with azathioprine.
Cattan
S
S
Service de Gastroentérologie, Hôpital Saint-Louis, Paris.
Lémann
M
M
Thuillier
F
F
Bengoufa
D
D
Rabian
C
C
Ngo
Y
Y
Bouhnik
Y
Y
Messing
B
B
Rambaud
J C
JC
Modigliani
R
R
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007700:Kinetics; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008297:Male; D015122:Mercaptopurine / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis
D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D015122:Mercaptopurine; D001379:Azathioprine
Dosage de la 6-mercaptopurine et étude des sous-populations lymphocytaires sanguines au cours du traitement par l'azathioprine dans la malaide de Crohn.