Steady-state of azathioprine during initiation treatment of pediatric inflammatory bowel disease
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21122571
DOI
10.1016/j.crohns.2010.06.005
PII: S1873-9946(10)00095-4
Knihovny.cz E-resources
- MeSH
- Azathioprine metabolism pharmacokinetics therapeutic use MeSH
- Child MeSH
- Genotype MeSH
- Guanine Nucleotides blood pharmacokinetics MeSH
- Inflammatory Bowel Diseases drug therapy enzymology MeSH
- Immunosuppressive Agents metabolism pharmacokinetics therapeutic use MeSH
- Humans MeSH
- Mercaptopurine analogs & derivatives blood metabolism pharmacokinetics MeSH
- Methyltransferases genetics metabolism MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Prospective Studies MeSH
- Severity of Illness Index MeSH
- Thionucleotides blood pharmacokinetics MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 6-methylthiopurine MeSH Browser
- 6-thioguanylic acid MeSH Browser
- Azathioprine MeSH
- Guanine Nucleotides MeSH
- Immunosuppressive Agents MeSH
- Mercaptopurine MeSH
- Methyltransferases MeSH
- Thionucleotides MeSH
- thiopurine methyltransferase MeSH Browser
BACKGROUND AND AIM: Azathioprine (AZA) has a slow onset of action in treatment of pediatric inflammatory bowel disease (IBD). It is anticipated, that this delay correlates to the kinetics of 6-thioguanine nucleotides (6-TGN) accumulation. The aim of this study was to evaluate the time to steady state of 6-TGN concentration in red blood cells. METHODS: The inclusion criteria were: a) age 0-19 years b) IBD diagnosis c) AZA treatment initiation. High performance liquid chromatography was used for the 6-TGN analysis. Concentrations of metabolites were studied in weeks 0, 1, 2, 5, and 8 after beginning of treatment. RESULTS: The inclusion criteria were matched to 18 patients with IBD. The median time to steady state of 6-TGN was 55.3 days. The mean 6-TGN concentration at the steady state achieved 326 (SD 154) pmol/8.108 erythrocytes. High erythrocyte TPMT activity corresponds to the low steady state 6-TGN concentration and vice versa. This correlation reached statistical significance (p<0.01) for the dose expressed in mg per square meter of body surface area. CONCLUSION: The time to steady state of 6-TGN erythrocyte concentration is significantly shorter than would expected according to clinical observation describe earlier.
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