Gupta P, Gokhale R, Kirschner B S
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The University of Chicago Children's Hospital, Chicago, Illinois 60637, USA.
J Pediatr Gastroenterol Nutr. 2001 Oct;33(4):450-4. doi: 10.1097/00005176-200110000-00006.
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.
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.
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).
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.
一些作者认为，6-巯基嘌呤（6-MP）对炎症性肠病患者的疗效与循环6-硫鸟嘌呤（6-TG）水平的相关性，超过235 pmol/8×10⁸红细胞。作者评估了炎症性肠病儿童和青少年中6-MP代谢物水平与疾病活动度之间的关系。
测定了来自单一中心的101例炎症性肠病儿童的临床状态、血液学和肝脏参数，并与6-MP代谢物水平进行比较。
缓解期患者的6-TG水平有高于活动期患者的趋势（217对173）；然而，差异无统计学意义（P = 0.09）。当6-TG水平大于235 pmol/8×10⁸红细胞时，治疗反应的可能性并未显著增加（优势比1.7；P = 0.1）。在本研究中，58%的缓解期患者6-TG水平低于235。然而，对50例活动期疾病患者的6-MP代谢物水平进行连续测量显示，在纵向随访的患者中，6-TG水平升高与疾病缓解显著相关（P = 0.04）。白细胞减少与高6-TG水平显著相关（P = 0.03），但与临床反应无关（P = 0.2）。
这些数据表明，其他人先前描述的6-TG水平目标范围不适用于58%处于缓解期的儿科炎症性肠病患者。然而，对患有活动期疾病的个体患者进行6-MP代谢物水平的连续监测，应能在使毒性风险最小化的同时提高剂量并诱导缓解。
