Abstract | BACKGROUND: METHODS: This study explored the relationship between the weight-based dosage of AZA and metabolites levels in 86 pediatric IBD patients using multilevel analysis. Other covariates related to patient characteristics and treatment were evaluated. RESULTS: This is the first study to demonstrate positive correlations between AZA dose and 6-TGN and 6-MeMPN levels and 6-MeMPN/6-TGN ratio (P < 0.001) in IBD children. Other novel predictors of metabolites were reported. Younger children exhibited lower 6-TGN and 6-MeMPN levels, probably suggesting age-related differences in metabolism and/or absorption of thiopurines. Coadministration of infliximab resulted in a significant increase in 6-TGN levels (P = 0.023). Moreover, alanine aminotransferase values positively correlated with 6-MeMPN levels (P = 0.032). The duration of AZA therapy, gender, and thiopurine methyltransferase activity were associated with metabolite levels. The wide interindividual variability in metabolite levels that accounted for 67.7%, 48.6%, and 49.4% of variance in the 6-TGN and 6-MeMPN levels and the ratio, respectively, were confirmed. CONCLUSIONS: The reliable AZA dose-metabolites relationship is useful for clinicians to guide the dosing regimen to maximize clinical response and minimize side effects or to consider alternative therapies when patients have preferential production of the toxic 6-MeMPN. These results may be of potential interest for optimizing thiopurine therapy to achieve safe and efficacious AZA use in pediatric IBD patients.
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Authors | Thi-Van-Anh Nguyen, Dinh H Vu, Thi-Mai-Hoang Nguyen, Alain Lachaux, Roselyne Boulieu |
Journal | Therapeutic drug monitoring
(Ther Drug Monit)
Vol. 35
Issue 2
Pg. 251-7
(Apr 2013)
ISSN: 1536-3694 [Electronic] United States |
PMID | 23503453
(Publication Type: Journal Article)
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Chemical References |
- Guanine Nucleotides
- Immunosuppressive Agents
- Thionucleotides
- 6-thioguanylic acid
- 6-methylthiopurine
- Mercaptopurine
- Azathioprine
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Topics |
- Adolescent
- Age Factors
- Azathioprine
(administration & dosage)
- Child
- Dose-Response Relationship, Drug
- Female
- Guanine Nucleotides
(metabolism)
- Humans
- Immunosuppressive Agents
(administration & dosage)
- Inflammatory Bowel Diseases
(drug therapy, metabolism)
- Male
- Mercaptopurine
(analogs & derivatives, metabolism)
- Multilevel Analysis
(methods)
- Retrospective Studies
- Thionucleotides
(metabolism)
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