药物基因组学和药物蛋白质组学杂志

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Thiopurine Methyltransferase Genotype Testing in Paediatric Patients in South Australia. A Retrospective Audit into Prescribing Practices.

Mahindroo S, Fletcher J, Hissaria P, Hakendorf P, Nicholson S.

Background: Thiopurines are used to treat a number of medical conditions including inflammatory bowel disease, acute lymphoblastic leukemia and severe eczema in children. Pre prescription identification of variant alleles helps reduce thiopurine related adverse events. The aim of the study was to explore the clinical utility of TPMT genotyping in a paediatric population in South Australia, specifically the uptake of testing and whether the results are guiding appropriate dosing of thiopurines in keeping with current established international guidelines. Methods: A retrospective audit was conducted reviewing all patients below the age of 18 years who underwent TPMT genotyping in South Australia during the 10-year period between January 2004 and January 2014. Data regarding demographics and prescribing practices was collected from the medical records of 260 paediatric patients. Results: Paediatric gastroenterologists requested 67% of the TPMT genotypes performed. Loss of function alleles were confirmed in almost 9% of cases. There were positive correlations between adverse events and whether the test was used correctly (p 0.011) and with subspecialty unit (p<0.001). Oncology recorded the largest percentage of adverse events 63.5% whilst only comprising 16.5% of the total dataset. Conclusion: The safest prescribing practice in all groups of patients is to ensure the TPMT gentyope is performed prior to administration and dosing is guided by the results and established guidelines.