PMID- 22697075
OWN - NLM
STAT- MEDLINE
DCOM- 20120724
LR  - 20191210
IS  - 0394-6320 (Print)
IS  - 0394-6320 (Linking)
VI  - 25
IP  - 2
DP  - 2012 Apr-Jun
TI  - A validated HPLC method for the monitoring of thiopurine metabolites in whole 
      blood in paediatric patients with inflammatory bowel disease.
PG  - 435-44
AB  - 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.
FAU - Cangemi, G
AU  - Cangemi G
AD  - Clinical Pathology Laboratory Unit, Giannina Gaslini Institute, Genoa, Italy. 
      giulianacangemi@ospedale-gaslini.ge.it
FAU - Barabino, A
AU  - Barabino A
FAU - Barco, S
AU  - Barco S
FAU - Parodi, A
AU  - Parodi A
FAU - Arrigo, S
AU  - Arrigo S
FAU - Melioli, G
AU  - Melioli G
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Validation Study
PL  - England
TA  - Int J Immunopathol Pharmacol
JT  - International journal of immunopathology and pharmacology
JID - 8911335
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Gastrointestinal Agents)
RN  - 6V404DV25O (6-methylthiopurine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - FTK8U1GZNX (Thioguanine)
SB  - IM
MH  - Adolescent
MH  - Age Factors
MH  - Anti-Inflammatory Agents/blood/*pharmacokinetics/therapeutic use
MH  - Biotransformation
MH  - Child
MH  - Child, Preschool
MH  - *Chromatography, High Pressure Liquid
MH  - Drug Monitoring/*methods
MH  - Erythrocytes/metabolism
MH  - Female
MH  - Gastrointestinal Agents/blood/*pharmacokinetics/therapeutic use
MH  - Humans
MH  - Infant
MH  - Inflammatory Bowel Diseases/blood/*drug therapy
MH  - Italy
MH  - Male
MH  - Mercaptopurine/*analogs & derivatives/blood/pharmacokinetics/therapeutic use
MH  - Reproducibility of Results
MH  - Thioguanine/blood/*pharmacokinetics/therapeutic use
EDAT- 2012/06/16 06:00
MHDA- 2012/07/25 06:00
CRDT- 2012/06/16 06:00
PHST- 2012/06/16 06:00 [entrez]
PHST- 2012/06/16 06:00 [pubmed]
PHST- 2012/07/25 06:00 [medline]
AID - 13 [pii]
AID - 10.1177/039463201202500213 [doi]
PST - ppublish
SO  - Int J Immunopathol Pharmacol. 2012 Apr-Jun;25(2):435-44. doi: 
      10.1177/039463201202500213.