Document Detail

Monitoring of azathioprine metabolites in pediatric patients with autoimmune hepatitis.
MedLine Citation:
PMID:  20479703     Owner:  NLM     Status:  MEDLINE    
Azathioprine is commonly used in the treatment of autoimmune hepatitis (AIH). Few data are available on drug monitoring of azathioprine metabolites in patients with AIH, especially in pediatric patients. The purpose of this study was to investigate intracellular thiopurine metabolites in children with AIH and to assess the relevance of drug monitoring compared with the efficacy and toxicity. Data from 28 patients with AIH treated by azathioprine for at least 3 months were recorded. 6-Thioguanine nucleotides (6-TGN) and 6-methyl mercaptopurine nucleotides (6-MeMPN) concentrations and TPMT activity were determined by high-performance liquid chromatography. Blood cell counts and liver function tests were also collected and the clinical outcome was documented. A wide interindividual variability in 6-TGN and 6-MeMPN concentrations was observed with values ranging from 51 to 1966 pmol/8 x 10(8) red blood cells (RBCs) for 6-TGN and from 42 to 8189 pmol/8 x 10(8) RBCs for 6-MeMPN. A total of 61.4% of the patients achieved remission and only 32.6% of these children had 6-TGN values within the target range proposed for inflammatory bowel disease (250-450 pmol/8 x 10(8) red blood cells). No difference in metabolite concentrations was observed between children in remission and those with active disease. Azathioprine dosage was significantly related to 6-TGN and 6-MeMPN levels (r = 0.308, P < 0.001 and r = 0.405, P < 0.001, respectively). A significant negative correlation was observed between 6-TGN concentrations and erythrocyte and lymphocyte counts, whereas 6-MeMPN was not related to blood cell counts. Although leukocyte counts were not related to 6-TGN concentrations, patients with leucopenia exhibited higher 6-TGN values than those without leucopenia (median values 438 pmol/8 x 10(8) RBCs versus 405 pmol/8 x 10(8) RBCs, respectively). Thiopurine metabolite monitoring appears useful in identifying the myelotoxicity and the hepatotoxicity as a result of azathioprine with disease recurrence and to assess adherence to therapy. A further larger study will be required to confirm the optimal recommended target for thiopurine metabolites to achieve remission in patients with AIH.
Thi-Mai-Hoang Nguyen; Marina Daubard; Catherine Le Gall; Magali Larger; Alain Lachaux; Roselyne Boulieu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Therapeutic drug monitoring     Volume:  32     ISSN:  1536-3694     ISO Abbreviation:  Ther Drug Monit     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-28     Completed Date:  2010-11-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7909660     Medline TA:  Ther Drug Monit     Country:  United States    
Other Details:
Languages:  eng     Pagination:  433-7     Citation Subset:  IM    
Université de Lyon, Département de Pharmacie Clinique, de Pharmacocinétique et d'Evaluation du Médicament, Lyon, France.
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MeSH Terms
6-Mercaptopurine / analogs & derivatives,  blood
Adrenal Cortex Hormones / therapeutic use
Anti-Inflammatory Agents / therapeutic use
Azathioprine / adverse effects,  pharmacokinetics*,  therapeutic use*
Blood Cell Count
Child, Preschool
Chromatography, High Pressure Liquid
Drug Monitoring
Drug Therapy, Combination
Hepatitis, Autoimmune / blood*,  drug therapy*
Immunosuppressive Agents / adverse effects,  pharmacokinetics*,  therapeutic use*
Liver Function Tests
Thioguanine / blood
Reg. No./Substance:
0/Adrenal Cortex Hormones; 0/Anti-Inflammatory Agents; 0/Immunosuppressive Agents; 154-42-7/Thioguanine; 446-86-6/Azathioprine; 50-44-2/6-Mercaptopurine; 50-66-8/6-methylthiopurine

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

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