Abstract | BACKGROUND: Measuring levels of 6-mercaptopurine (6-MP) metabolites ( 6-thioguanine nucleotides [6-TGNs] and 6- methylmercaptopurine [6- MMP]) has been proposed as a method to adjust 6-MP dose to optimize therapeutic response while minimizing toxicity in patients with inflammatory bowel disease. A 6-TGN level of >230 pmol/8 x 108 red blood cells (RBCs) has been reported to be associated with a higher efficacy rate, and a level of >450 pmol/8 x 108 RBCs has been reported to be associated with myelotoxicity. A 6-MMP level of >5,700 pmol/8 x 108 RBCs has been reported to be associated with an increased frequency of abnormal results of liver function tests (LFTs). GOALS: To report our experience with 6-MMP and 6-TGN levels in a clinical practice setting. STUDY: Using outpatient clinic medical records, we identified 53 measurements. Indications for measurement, 6-MP dose, and subsequent adjustments were documented. RESULTS: Indications for measurements included the following: persistent symptoms, 31 cases (58.5%); abnormal LFT results, 7 (13.2%); steroid dependency, 6 (11.3%); anemia, 4 (7.5%); and leukopenia, 2 (3.8%). Of the 31 cases with persistent symptoms, 12 had "therapeutic" 6-TGN levels and other interventions were undertaken. 6-TGN levels were "subtherapeutic" in 19. The 6-MP dose was increased, and remission was achieved in 10 cases after a mean period of 3.6 weeks. Among the cases with abnormal LFT results, 6-MMP levels were high in five and low in two. Among the steroid dependency cases, 6-TGN levels were "subtherapeutic" in five. The dose was increased and steroids were weaned in three cases. The 6-TGN level was high in one of the leukopenia cases and the 6-MP dose was decreased. 6-TGN levels were not above the "target range" in any of the anemia cases. CONCLUSION: Measuring levels of 6-MP metabolites may have a role in customizing 6-MP dosing. This role is not completely clear and needs to be explored in larger well-controlled studies.
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Authors | Houssam E Mardini, George L Arnold |
Journal | Journal of clinical gastroenterology
(J Clin Gastroenterol)
2003 May-Jun
Vol. 36
Issue 5
Pg. 390-5
ISSN: 0192-0790 [Print] United States |
PMID | 12702978
(Publication Type: Journal Article)
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Chemical References |
- Guanine Nucleotides
- Immunosuppressive Agents
- Thionucleotides
- 6-thioguanylic acid
- 6-methylthiopurine
- Mercaptopurine
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Female
- Guanine Nucleotides
(metabolism)
- Humans
- Immunosuppressive Agents
(administration & dosage, metabolism, therapeutic use)
- Inflammatory Bowel Diseases
(drug therapy, metabolism)
- Male
- Mercaptopurine
(administration & dosage, analogs & derivatives, metabolism, therapeutic use)
- Middle Aged
- Retrospective Studies
- Thionucleotides
(metabolism)
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