Cuffari C, Seidman E G, Latour S, Théorêt Y
Department of Pediatrics, Hôpital Sainte-Justine, Université de Montréal, QC, Canada.
Can J Physiol Pharmacol. 1996 May;74(5):580-5.
The effects of 6-mercaptopurine (6MP) in inflammatory bowel disease are believed to be primarily mediated by its metabolite 6-thioguanine (6TG). Our aim was to develop an assay for measuring leukocyte DNA 6TG levels in patients with Crohn's disease, and to correlate them with levels of 6TG in erythrocytes. Heparinized blood was obtained from 15 adolescent Crohn's disease patients receiving 6MP at an average dose of 1.3 mg.kg-1 day-1 (range 0.8-1.6 mg.kg-1 day-1) for a mean of 23.7 months (range 3-71 months). Leukocyte DNA and erythrocyte 6TG levels were measured by an HPLC assay. Leukocyte 6TG levels ranged from 100 to 2305 pmol/mg DNA, while erythrocyte 6TG levels ranged from 64 to 1038 pmol/8 x 10(8) red blood cells, demonstrating significant interpatient variability. Leukocyte DNA 6TG levels correlated directly with erythrocyte 6TG levels, as measured by the Spearman rank correlation coefficient (p < 0.05). The HPLC measurement of erythrocyte and leukocyte DNA 6TG levels can be useful clinically in monitoring compliance, as well as perhaps to tailor drug metabolite levels to achieve the desired clinical effect.
6-巯基嘌呤（6MP）在炎症性肠病中的作用被认为主要是由其代谢产物6-硫鸟嘌呤（6TG）介导的。我们的目的是开发一种检测克罗恩病患者白细胞DNA中6TG水平的方法，并将其与红细胞中6TG水平相关联。从15名接受6MP治疗的青少年克罗恩病患者中获取肝素化血液，这些患者的平均剂量为1.3mg·kg-1·天-1（范围为0.8 - 1.6mg·kg-1·天-1），平均治疗时间为23.7个月（范围为3 - 71个月）。通过高效液相色谱法（HPLC）检测白细胞DNA和红细胞6TG水平。白细胞6TG水平范围为100至2305pmol/mg DNA，而红细胞6TG水平范围为64至1038pmol/8×10⁸个红细胞，表明患者间存在显著差异。通过Spearman等级相关系数测量，白细胞DNA 6TG水平与红细胞6TG水平直接相关（p < 0.05）。红细胞和白细胞DNA 6TG水平的HPLC测量在临床上可用于监测依从性，也可能有助于调整药物代谢产物水平以达到预期的临床效果。
