Monitoring of thiopurine metabolites in patients with inflammatory bowel disease-what is actually measured?

Therapeutic Drug Monitoring

Volumn 31, Issue 3, 2009, Pages 345-350

  Vikingsson, Svante ^a,c   Carlsson, Björn ^a   Almer, Sven Hc ^b   Peterson, Curt ^a  

^a Division of Drug Research   (Sweden)

^b LINKÖPING UNIVERSITY   (Sweden)

^c LINKÖPING UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Inflammatory bowel disease; Therapeutic drug monitoring; Thiopurines

Indexed keywords

6 THIOGUANOSINE NUCLEOTIDE; AZATHIOPRINE; DRUG METABOLITE; GUANOSINE PHOSPHATE; MERCAPTOPURINE; METHYLMERCAPTOPURINE; METHYLTHIOINOSINE MONOPHOSPHATE; THIOGUANOSINE DIPHOSPHATE; THIOGUANOSINE MONOPHOSPHATE; THIOGUANOSINE TRIPHOSPHATE; TIOGUANINE; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG HYDROLYSIS; DRUG MONITORING; ENTERITIS; ERYTHROCYTE; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; MALE; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS;

6-MERCAPTOPURINE; ADULT; AGED; AGED, 80 AND OVER; AZATHIOPRINE; DRUG MONITORING; FEMALE; HUMANS; INFLAMMATORY BOWEL DISEASES; MALE; MIDDLE AGED; YOUNG ADULT;

EID: 67651100777     PISSN: 01634356     EISSN: 15363694     Source Type: Journal    
DOI: 10.1097/FTD.0b013e3181a1ea58     Document Type: Article

References (28)

1. Sandborn W, Sutherland L, Pearson D, et al. Azathioprine or 6- mercaptopurine for inducing remission of Crohn's disease. Cochrane Database Syst Rev. 2000:CD000545.
2. Lennard L. The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol. 1992;43:329-339.
3. Coulthard S, Hogarth L. The thiopurines: an update. Invest New Drugs. 2005;23:523-532.
4. Karran P, Attard N. Thiopurines in current medical practice: molecular mechanisms and contributions to therapy-related cancer. Nat Rev Cancer. 2008;8:24-36.
5. Tiede I, Fritz G, Strand S, et al. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest. 2003;111:1133-1145.
6. Evans WE, Horner M, Chu YQ, et al. Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase- deficient child with acute lymphocytic leukemia. J Pediatr. 1991;119:985-989.
7. Stet EH, De Abreu RA, Bokkerink JP, et al. Decrease in Sadenosylmethionine synthesis by 6-mercaptopurine and methylmercaptopurine ribonucleoside in Molt F4 human malignant lymphoblasts. Biochem J. 1994;304(Pt 1):163-168.
8. Lindqvist M, Hindorf U, Almer S, et al. Thiopurines in inflammatory bowel disease-the role of pharmacogenetics and therapeutic drug monitoring. Curr Pharmacogenomics. 2006;4:16.
9. Hindorf U, Lindqvist M, Peterson C, et al. Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. Gut. 2006;55:1423-1431.
10. Lennard L, Singleton HJ. High-performance liquid chromatographic assay of the methyl and nucleotide metabolites of 6-mercaptopurine: quantitation of red blood cell 6-thioguanine nucleotide, 6-thioinosinic acid and 6-methylmercaptopurine metabolites in a single sample. J Chromatogr. 1992;583:83-90.
11. Dervieux T, Boulieu R. Simultaneous determination of 6-thioguanine and methyl 6-mercaptopurine nucleotides of azathioprine in red blood cells by HPLC. Clin Chem. 1998;44:551-555.
12. Dervieux T, Boulieu R. Identification of 6-methylmercaptopurine derivative formed during acid hydrolysis of thiopurine nucleotides in erythrocytes, using liquid chromatography-mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance assay. Clin Chem. 1998;44:2511-2515.
13. Boulieu R, Bory C, Gonnet C. Liquid-chromatographic measurement of purine nucleotides in blood cells. Clin Chem. 1985;31:727-731.
14. Herrlinger KR, Fellermann K, Fischer C, et al. Thioguanine-nucleotides do not predict efficacy of thioguanine in Crohn's disease. Aliment Pharmacol Ther. 2004;19:1269-1276.
15. Lowry PW, Franklin CL, Weaver AL, et al. Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease. Gut. 2001;49:665-670.
16. Osterman MT, Kundu R, Lichtenstein GR, et al. Association of 6- thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology. 2006;130:1047-1053.
17. Lennard L. Assay of 6-thioinosinic acid and 6-thioguanine nucleotides, active metabolites of 6-mercaptopurine, in human red blood cells. J Chromatogr. 1987;423:169-178.
18. Pettersson B, Almer S, Albertioni F, et al. Differences between children and adults in thiopurine methyltransferase activity and metabolite formation during thiopurine therapy: possible role of concomitant methotrexate. Ther Drug Monit. 2002;24:351-358.
19. Haglund S, Taipalensuu J, Peterson C, et al. IMPDH activity in thiopurinetreated patients with inflammatory bowel disease-relation to TPMT activity and metabolite concentrations. Br J Clin Pharmacol. 2008;65: 69-77.
20. Hindorf U, Peterson C, Almer S. Assessment of thiopurine methyltransferase and metabolite formation during thiopurine therapy: results from a large Swedish patient population. Ther Drug Monit. 2004;26: 673-678.
21. Rabel SR, Stobaugh JF, Trueworthy R. Determination of intracellular levels of 6-mercaptopurine metabolites in erythrocytes utilizing capillary electrophoresis with laser-induced fluorescence detection. Anal Biochem. 1995;224:315-322.
22. Neurath MF, Kiesslich R, Teichgraber U, et al. 6-thioguanosine diphosphate and triphosphate levels in red blood cells and response to azathioprine therapy in Crohn's disease. Clin Gastroenterol Hepatol. 2005;3:1007-1014.
23. Finkel JM. Fluorometric assay of thioguanine. J Pharm Sci. 1975;64: 121-122.
24. Shipkova M, Armstrong VW, Wieland E, et al. Differences in nucleotide hydrolysis contribute to the differences between erythrocyte 6-thioguanine nucleotide concentrations determined by two widely used methods. Clin Chem. 2003;49:260-268.
25. Lavi LE, Holcenberg JS. A rapid and sensitive high-performance liquid chromatographic assay for 6-mercaptopurine metabolites in red blood cells. Anal Biochem. 1985;144:514-521.
26. Giverhaug T, Bergan S, Loennechen T, et al. Analysis of methylated 6-mercaptopurine metabolites in human red blood cells: comparison of two methods. Ther Drug Monit. 1997;19:663-668.
27. Keuzenkamp-Jansen CW, De Abreu RA, Bokkerink JP, et al. Determination of extracellular and intracellular thiopurines and methylthiopurines by high-performance liquid chromatography. J Chromatogr B Biomed Appl. 1995;672:53-61.
28. Gilissen LP, Derijks LJ, Bos LP, et al. Therapeutic drug monitoring in patients with inflammatory bowel disease and established azathioprine therapy. Clin Drug Investig. 2004;24:479-486.