P Gupta1, R Gokhale, B S Kirschner. 1. Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The University of Chicago Children's Hospital, Chicago, Illinois 60637, USA. pgupta@peds.bsd.uchicago.edu
Abstract
OBJECTIVES: Some authors suggest that efficacy of 6-mercaptopurine (6-MP) in patients with inflammatory bowel disease correlates with circulating 6-thioguanine (6-TG) levels more than 235 pmol/8 x 10(8) red blood cells. The authors evaluated the relation between 6-MP metabolite levels and disease activity in children and adolescents with inflammatory bowel disease. METHODS: Clinical status and hematologic and hepatic parameters were determined in 101 children with inflammatory bowel disease from a single center and compared with 6-MP metabolite levels. RESULTS: There was a trend for higher 6-TG levels among patients in remission than among those with active disease (217 vs. 173); however the difference was not statistically significant ( P = 0.09). The likelihood of therapeutic response did not increase significantly at 6-TG levels greater than 235 pmol/8 x 10(8) red blood cells (odds ratio 1.7; P = 0.1). In the current study, 58% of patients in remission had 6-TG levels less than 235. However, serial measurements of 6-MP metabolite levels in 50 patients with active disease showed that increasing 6-TG levels correlated significantly with disease remission in patients followed up longitudinally ( P = 0.04). Leukopenia was significantly associated with high 6-TG levels ( P = 0.03) but not with clinical response ( P = 0.2). CONCLUSIONS: These data suggest that the target range of 6-TG levels previously described by others did not apply to 58% of the pediatric patients with IBD in remission. However, serial monitoring of 6-MP metabolite levels in individual patients with active disease should allow dose escalation and induction of remission while minimizing the risk of toxicity.
OBJECTIVES: Some authors suggest that efficacy of 6-mercaptopurine (6-MP) in patients with inflammatory bowel disease correlates with circulating 6-thioguanine (6-TG) levels more than 235 pmol/8 x 10(8) red blood cells. The authors evaluated the relation between 6-MP metabolite levels and disease activity in children and adolescents with inflammatory bowel disease. METHODS: Clinical status and hematologic and hepatic parameters were determined in 101 children with inflammatory bowel disease from a single center and compared with 6-MP metabolite levels. RESULTS: There was a trend for higher 6-TG levels among patients in remission than among those with active disease (217 vs. 173); however the difference was not statistically significant ( P = 0.09). The likelihood of therapeutic response did not increase significantly at 6-TG levels greater than 235 pmol/8 x 10(8) red blood cells (odds ratio 1.7; P = 0.1). In the current study, 58% of patients in remission had 6-TG levels less than 235. However, serial measurements of 6-MP metabolite levels in 50 patients with active disease showed that increasing 6-TG levels correlated significantly with disease remission in patients followed up longitudinally ( P = 0.04). Leukopenia was significantly associated with high 6-TG levels ( P = 0.03) but not with clinical response ( P = 0.2). CONCLUSIONS: These data suggest that the target range of 6-TG levels previously described by others did not apply to 58% of the pediatric patients with IBD in remission. However, serial monitoring of 6-MP metabolite levels in individual patients with active disease should allow dose escalation and induction of remission while minimizing the risk of toxicity.
Authors: Alexander Teml; Elke Schaeffeler; Klaus R Herrlinger; Ulrich Klotz; Matthias Schwab Journal: Clin Pharmacokinet Date: 2007 Impact factor: 5.577