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Steady-state of azathioprine during initiation treatment of pediatric inflammatory bowel disease

O Pozler1, J Chládek, J Malý

  • 1Dept. of Pediatrics, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Králové, Czech Republic. pozler@lfhk.cuni.cz

Journal of Crohn'S & Colitis
|December 3, 2010
PubMed

Insights

The time for 6-thioguanine nucleotides (6-TGN) to reach steady-state levels in red blood cells during azathioprine (AZA) treatment for pediatric inflammatory bowel disease (IBD) is shorter than clinically expected. This finding impacts treatment monitoring for pediatric IBD patients.

Area of Science:

  • Pharmacology
  • Pediatric Gastroenterology
  • Immunosuppression

Background:

  • Azathioprine (AZA) exhibits a delayed onset of action in treating pediatric inflammatory bowel disease (IBD).
  • This delay is hypothesized to be linked to the time required for 6-thioguanine nucleotide (6-TGN) accumulation.
  • Understanding 6-TGN kinetics is crucial for optimizing AZA therapy in children.

Purpose of the Study:

  • To determine the time to achieve steady-state concentrations of 6-thioguanine nucleotides (6-TGN) in red blood cells.
  • To correlate 6-TGN levels with thiopurine S-methyltransferase (TPMT) activity in pediatric IBD patients on AZA.

Main Methods:

  • Study included 18 pediatric patients (0-19 years) diagnosed with IBD initiating AZA treatment.
  • Red blood cell 6-TGN concentrations were analyzed using high-performance liquid chromatography at weeks 0, 1, 2, 5, and 8.
  • Erythrocyte TPMT activity was assessed and correlated with 6-TGN levels.

Main Results:

  • The median time to reach steady-state 6-TGN concentration was 55.3 days.
  • The mean steady-state 6-TGN concentration was 326 pmol/8.108 erythrocytes.
  • A statistically significant inverse correlation (p<0.01) was observed between TPMT activity and steady-state 6-TGN levels, particularly when AZA dose was normalized to body surface area.

Conclusions:

  • The time to achieve steady-state 6-TGN erythrocyte concentration is significantly shorter than previously suggested by clinical observations.
  • These findings provide valuable pharmacokinetic data for monitoring AZA therapy in pediatric IBD.
  • Understanding 6-TGN kinetics can aid in more timely therapeutic adjustments for improved patient outcomes.
Abstract

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