Evaluating the use of metabolite measurement in children receiving treatment with a thiopurine
Article first published online: 19 SEP 2011
© 2011 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 34, Issue 9, pages 1106–1114, November 2011
How to Cite
Armstrong, L., Sharif, J.-A., Galloway, P., McGrogan, P., Bishop, J. and Russell, R. K. (2011), Evaluating the use of metabolite measurement in children receiving treatment with a thiopurine. Alimentary Pharmacology & Therapeutics, 34: 1106–1114. doi: 10.1111/j.1365-2036.2011.04848.x
- Issue published online: 10 OCT 2011
- Article first published online: 19 SEP 2011
- Publication data Submitted 31 January 2011 First decision 19 February 2011 Resubmitted 14 August 2011 Accepted 18 August 2011 EV Pub Online 19 September 2011
Aliment Pharmacol Ther 2011; 34: 1106–1114
Background Clinical response to thiopurine medication is related to the concentration of its metabolites. Proxy measures are traditionally used to assess dose adequacy. We present our experience of using tioguanine (previously known/formerly referred to as thioguanine) metabolite measurements in paediatric patients and evaluate their effect on clinical practice.
Aims To report our experience of using tioguanine metabolite measurements in paediatric patients and to evaluate their effects on clinical practice.
Methods The 6-tioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) were measured in children prescribed thiopurine medication for at least 3 months. Data were collected on thiopurine methyl transferase (TPMT) genotype, drug dose, laboratory indices and management changes. Therapeutic 6-TGN levels were defined as 235–400 pmol/8 × 108 RBCs. Seventy individuals (30 males) with a median age of 15 years. Underlying diagnoses were ‘IBD’ (68/70) and two cases of eosinophilic colitis. Sixty-three were treated with azathioprine and seven with mercaptopurine. A total of 103 separate measurements were made.
Results On initial measurement, 68% of patients had 6-TGN levels outside therapeutic levels despite standard thiopurine dosing. Initial 6-TGN levels were significantly higher in patients with TPMT mutations. Toxicity occurred in seven cases. The 6-TGN levels were significantly higher in those with signs of marrow toxicity. The 6-TGN level correlated with WBC, leukocyte count, mean corpuscular volume (MCV) and ΔMCV; however, the ability of each of these to predict therapeutic 6-TGN levels was poor. After initial measurement, management was changed in 25/70 cases (36%).
Conclusions 6-TGN levels were therapeutic in a minority of those patients who were tested. Proxy measures perform poorly in predicting therapeutic 6-TGN levels. Measuring thiopurine metabolites is useful for dosage adjustment in children, and for the detection of potential toxicity.