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Nicole M Giamanco, Bethany S Cunningham, Laura S Klein, Dina S Parekh, Anne B Warwick, Kenneth Lieuw
6-Mercaptopurine (6-MP) is the mainstay of treatment for acute lymphoblastic leukemia and lymphoblastic lymphoma. It is metabolized into the pharmacologically active, 6-thioguanine nucleotide (6-TGN), and 6-methyl mercaptopurine nucleotides (6-MMPN), which is associated with hepatotoxicity that jeopardizes antileukemic therapy. Allopurinol alters the metabolism of 6-MP to increase 6-TGN levels and decreases 6-methyl mercaptopurine nucleotides levels. We report 2 cases in which combination therapy of allopurinol with 6-MP was used successfully to avoid hepatotoxicity while delivering adequate 6-TGN levels...
March 2016: Journal of Pediatric Hematology/oncology
Laurent Chouchana, Celine Narjoz, Denis Roche, Jean-Louis Golmard, Brigitte Pineau, Gilles Chatellier, Philippe Beaune, Marie-Anne Loriot
BACKGROUND & AIMS: TPMT activity and metabolite determination (6-thioguanine nucleotides [6-TGN] and 6-methylmercaptopurine nucleotides [6-MMPN]) remain controversial during thiopurine management. This study assessed associations between patient characteristics and TPMT activity, and their impact on metabolite levels. PATIENTS & METHODS: A retrospective review of the laboratory database from a French university hospital identified 7360 patients referred for TPMT phenotype/genotype determination, and/or for 6-TGN/6-MMPN monitoring...
April 2014: Pharmacogenomics
Julienne Brackett, Eric S Schafer, Daniel H Leung, M Brooke Bernhardt
Mercaptopurine (6-MP), a critical component of acute lymphoblastic leukemia (ALL) therapy, is metabolized to 6-thioguanine (6-TGN) which is responsible for its anti-leukemic effect, and to 6-methylmercaptopurine nucleotides (6-MMPN/6-MMP) which can be hepatotoxic. Some patients preferentially metabolize 6-MP to 6-MMPN which may increase the risk of liver injury, reduce serum levels of 6-TGN and potentially increase the risk of relapse. The addition of allopurinol to oral 6-MP has been shown to optimize metabolism towards 6-TGN in patients with inflammatory bowel disease (IBD); however, this use has not been reported in patients undergoing treatment for ALL...
June 2014: Pediatric Blood & Cancer
Tiphaine Adam de Beaumais, May Fakhoury, Yves Medard, Said Azougagh, Daolun Zhang, Karima Yakouben, Evelyne Jacqz-Aigrain
AIMS: 6-mercaptopurine (6-MP) is used in the treatment of childhood acute lymphoblastic leukaemia (ALL). Its red blood cell (RBC) metabolite concentrations (6-thioguanine [6-TGN] and 6-methylmercaptopurine nucleotides [6-MMPN]) are related to drug response. We investigated the impact of non-genetic covariates and pharmacogenetic polymorphisms affecting thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) on 6-MP metabolism and response. METHODS: Sixty-six children with ALL treated according to EORTC 58951 protocol were included in this study...
April 2011: British Journal of Clinical Pharmacology
Sharon J Gardiner, Richard B Gearry, Michael J Burt, Teresa Chalmers-Watson, Bruce A Chapman, Alison G Ross, Catherine A M Stedman, Alexander Huelsen, Murray L Barclay
BACKGROUND AND AIM: Allopurinol potentiates azathioprine and 6-mercaptopurine (6-MP) by increasing 6-thioguanine nucleotide (6-TGN) metabolite concentrations. The outcome might also be improved by adding allopurinol in individuals who preferentially produce 6-methylmercaptopurine nucleotides (6-MMPN), rather than 6-TGN. The aim of the present study was to investigate the effect of allopurinol on concentrations of 6-MMPN and 6-TGN in individuals with a high ratio of these metabolites (>20), which is indicative of a poor thiopurine response...
January 2011: Journal of Gastroenterology and Hepatology
Sharon J Gardiner, Richard B Gearry, Michael J Burt, Steven L Ding, Murray L Barclay
Azathioprine and its initial metabolite, 6-mercaptopurine (6-MP), are associated with high rates of treatment cessation due to toxicity or inadequate response. Individualization of thiopurine dose based on concentrations of the active 6-thioguanine nucleotide (6-TGN) metabolites can help improve outcomes with this class. Some individuals, however, preferentially metabolize thiopurine drugs to the potentially hepatotoxic 6-methylmercaptopurine nucleotide (6-MMPN) metabolites rather than the 6-TGNs. For these patients, escalation in thiopurine dose is not likely to increase 6-TGN concentrations sufficiently but may lead to a disproportionate increase in exposure to the 6-MMPNs...
December 2008: European Journal of Gastroenterology & Hepatology
Kevin A Hommel, Christine M Davis, Robert N Baldassano
BACKGROUND: The objective was to examine the prevalence and frequency of oral medication nonadherence using a multimethod assessment approach consisting of objective, subjective, and biological data in adolescents with inflammatory bowel disease (IBD). METHODS: Medication adherence was assessed via pill counts, patient/parent interview, and 6-thioguanine nucleotide (6-TGN)/6-methylmercaptopurine nucleotide (6-MMPN) metabolite bioassay in 42 adolescents with IBD...
April 2009: Inflammatory Bowel Diseases
T N Witte, A L Ginsberg
BACKGROUND: At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN). PATIENTS AND METHODS: A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment...
February 2008: Canadian Journal of Gastroenterology, Journal Canadien de Gastroenterologie
Sharon J Gardiner, Richard B Gearry, Rebecca L Roberts, Mei Zhang, Murray L Barclay, Evan J Begg
AIMS: To determine infant exposure to 6-thioguanine and 6-methylmercaptopurine nucleotides (6-TGN and 6-MMPN, respectively) during maternal use of azathioprine in breastfeeding. METHODS: Mother-infant pairs provided blood for determination of 6-TGN and 6-MMPN concentrations, and TPMT genotype. RESULTS: Four women taking azathioprine 1.2-2.1 mg kg(-1) day(-1) and their infants were studied. All had the wild-type TPMT genotype. Maternal 6-TGN and 6-MMPN concentrations ranged from 234 to 291 and 284 to 1178 pmol per 8 x 10(8) red blood cells, respectively, and were consistent with those associated with improved therapeutic outcomes...
October 2006: British Journal of Clinical Pharmacology
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