6-MERCAPTOPURINE PHARMACOKINETICS AND BLO OD LYMPHOCYTE SUBPOPULATIONS IN PATIENTS WITH CROHNS-DISEASE TREATED WITH AZATHIOPRINE

Objectives. - Our aim was to study the relationships between clinical efficacy of azathioprine, 6-mercaptopurine pharmaco-kinetics and chang es in peripheral blood lymphocyte subpopulations induced by azathiopri ne 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+ lymph ocyte subpopulations were carried out, using flow cytometry, during az athioprine treatment. Pharmacokinetic studies were performed at day 8 and month 3 by measuring 6-mercaptopurine plasma concentration after a n oral dose of azathioprine (2 mg/kg). Results were compared in respon ders (no activity and no steroids) and non-responders. Results. - The decrease in-peripheral blood leukocytes and neutrophils was significan t 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 reac hed 41 % at 1 year. Percentages of CD3+, CD4+, CD8+, CD57+, CD16+CD56 and CD19+ lymphocytes remained unchanged whereas percentage of CD25lymphocytes increased from 10% to 28% (P<0.01). There was a high inter and intraindividual variability of 6-mercaptopurine peak plasma conce ntration and area under the curve. No significant difference was found between responders (n = 14) and non responders (n = 7) for pharmacoki netic parameters and lymphocyte subpopulations; there was no correlati on between lymphocyte subpopulation changes and 6-mercaptopurine pharm acokinetics. Conclusion. - Monitoring of 6-mercaptopurine plasma conce ntration and blood lymphocyte subpopulations is of little value in Cro hn's disease patients treated with azathioprine.