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A validated HPLC method for the monitoring of thiopurine metabolites in whole blood in paediatric patients with inflammatory bowel disease.
MedLine Citation:
PMID:  22697075     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Therapeutic drug monitoring (TDM) of major metabolites of thiopurine drugs is a widely used tool for assessing treatment efficacy and toxicity in patients with inflammatory bowel disease (IBD). We report the laboratory and clinical validation of a simple and reliable high performance liquid chromatography (HPLC) method for the measurement of 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) on paediatric patients with IBD. The aim of this paper is to develop and validate a method for the measurement of 6-TGN and 6-MMP applicable to routine practice and to evaluate the usefulness of the TDM of thiopurine drugs in children with IBD attending our Gastroenterology Unit. The HPLC method was validated following international guidelines starting from red blood cells (RBC) and whole blood (WB). A comparison between RBC and WB was assessed. The usefulness of TDM was then evaluated using the new method from WB in 47 paediatric patients with IBD treated with thiopurine drugs. WB and RBC resulted in interchangeable matrices. The majority of patients had the metabolite levels inside the therapeutic ranges. A moderate correlation was found between 6-MMP concentration and the dose of thiopurines. A higher percentage of non responders was found among patients with lower levels of 6-TGN. Toxicity was found in eight patients and was evaluated in respect to the metabolite concentration. The described HPLC method is applicable to routine practice and it is suitable for its use in multicentric studies. Our results of TDM on paediatric IBD patients can contribute to clarify its role in their therapeutic management.
Authors:
G Cangemi; A Barabino; S Barco; A Parodi; S Arrigo; G Melioli
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of immunopathology and pharmacology     Volume:  25     ISSN:  0394-6320     ISO Abbreviation:  Int J Immunopathol Pharmacol     Publication Date:    2012 Apr-Jun
Date Detail:
Created Date:  2012-06-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8911335     Medline TA:  Int J Immunopathol Pharmacol     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  435-44     Citation Subset:  IM    
Affiliation:
Clinical Pathology Laboratory Unit, Giannina Gaslini Institute, Genoa, Italy.
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