Achkar Jean-Paul, Stevens Tyler, Easley Kirk, Brzezinski Aaron, Seidner Douglas, Lashner Bret
Center for Inflammatory Bowel Disease, Departments of Gastroenterology and Biostatistics, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Inflamm Bowel Dis. 2004 Jul;10(4):339-45. doi: 10.1097/00054725-200407000-00003.
There is some uncertainty regarding how to best dose and therapeutically monitor 6-mercaptopurine or azathioprine in patients with inflammatory bowel disease. The purpose of this study was to assess the relation between clinical response, 6-mercaptopurine metabolite levels, relative leukopenia, and drug dose.
60 patients with inflammatory bowel disease who were on stable doses of 6-mercaptopurine or azathioprine for > or = 3 months and who had measurements of 6-mercaptopurine metabolite levels were evaluated. Patients were classified as complete responders (N = 24), partial responders (N = 7), or non-responders (N = 29).
Drug dose was associated with clinical response when we analyzed adjusted doses based on molecular drug weight (P = 0.002). 6-Thioguanine levels also were associated with clinical response (P = 0.003) and the maximal difference between responders and non-responders was seen at 6-thioguanine levels greater than 260 pmol/8 x 10(8) RBC. Relative leukopenia, defined as white blood cell count less than either 5.0 or 4.0 K/uL, was not associated with clinical response (P = 0.13 and 0.77 respectively).
对于炎症性肠病患者，如何最佳地确定6-巯基嘌呤或硫唑嘌呤的剂量以及进行治疗监测存在一定不确定性。本研究的目的是评估临床反应、6-巯基嘌呤代谢物水平、相对白细胞减少症和药物剂量之间的关系。
对60例接受稳定剂量的6-巯基嘌呤或硫唑嘌呤治疗≥3个月且已测定6-巯基嘌呤代谢物水平的炎症性肠病患者进行评估。患者被分为完全缓解者（N = 24）、部分缓解者（N = 7）或无反应者（N = 29）。
当我们根据分子药物重量分析调整剂量时，药物剂量与临床反应相关（P = 0.002）。6-硫鸟嘌呤水平也与临床反应相关（P = 0.003），在6-硫鸟嘌呤水平大于260 pmol/8×10⁸红细胞时，缓解者与无反应者之间的最大差异可见。定义为白细胞计数低于5.0或4.0 K/μL的相对白细胞减少症与临床反应无关（分别为P = 0.13和0.77）。
