R S Bloomfeld1, J E Onken. 1. Section of Gastroenterology, Wake Forest University Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC 27157, USA. rbloomfe@wfubmc.edu
Abstract
BACKGROUND: Azathioprine (AZA) and its active metabolite mercaptopurine (MP) are frequently used in the management of inflammatory bowel disease. Measurement of the AZA/MP metabolites, thioguanine (TG) and methylmercaptopurine (MMP), has been suggested as a means to optimize therapy with AZA/MP in inflammatory bowel disease. AIM: To evaluate the results of initial AZA/MP metabolite panels sent by gastroenterologists during the first year of its widespread availability. METHODS: Initial AZA/MP metabolite panels sent by gastroenterologists to a single laboratory were reviewed and the metabolite panels were interpreted. RESULTS: Initial metabolite levels were reviewed for 9187 patients. Noncompliance was detected in 263 patients (3%) and under-dosing in 4260 patients (46%). 534 patients (6%) had levels that were consistent with preferential metabolism via the TPMT pathway. The therapeutic goal was achieved in 2444 patients (27%) and an additional 552 patients (6%) had appropriate TG levels but potential hepatotoxicity. 936 patients (10%) had potential TPMT deficiency, and 58 patients (1%) had potential TPMT absence and were at risk for leukopenia. 140 patients (2%) had too high a dose. CONCLUSIONS: Measurement of AZA/MP metabolites can be used by practising gastroenterologists to identify potential reasons for nonresponse to AZA or MP, and to identify patients at risk for certain drug-related toxicities.
BACKGROUND:Azathioprine (AZA) and its active metabolite mercaptopurine (MP) are frequently used in the management of inflammatory bowel disease. Measurement of the AZA/MP metabolites, thioguanine (TG) and methylmercaptopurine (MMP), has been suggested as a means to optimize therapy with AZA/MP in inflammatory bowel disease. AIM: To evaluate the results of initial AZA/MP metabolite panels sent by gastroenterologists during the first year of its widespread availability. METHODS: Initial AZA/MP metabolite panels sent by gastroenterologists to a single laboratory were reviewed and the metabolite panels were interpreted. RESULTS: Initial metabolite levels were reviewed for 9187 patients. Noncompliance was detected in 263 patients (3%) and under-dosing in 4260 patients (46%). 534 patients (6%) had levels that were consistent with preferential metabolism via the TPMT pathway. The therapeutic goal was achieved in 2444 patients (27%) and an additional 552 patients (6%) had appropriate TG levels but potential hepatotoxicity. 936 patients (10%) had potential TPMT deficiency, and 58 patients (1%) had potential TPMT absence and were at risk for leukopenia. 140 patients (2%) had too high a dose. CONCLUSIONS: Measurement of AZA/MP metabolites can be used by practising gastroenterologists to identify potential reasons for nonresponse to AZA or MP, and to identify patients at risk for certain drug-related toxicities.
Authors: Virginia L Priest; Evan J Begg; Sharon J Gardiner; Christopher M A Frampton; Richard B Gearry; Murray L Barclay; David W J Clark; Paul Hansen Journal: Pharmacoeconomics Date: 2006 Impact factor: 4.981
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