Pharmacokinetics of 6-thioguanine in patients with inflammatory bowel disease
Pharmacokinetics of 6-thioguanine in patients with inflammatory bowel disease
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DOI：
10.1097/01.ftd.0000179839.71138.6d
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发表时间：
2006-02-01
影响因子：
2.5
通讯作者：
Hooymans, PM
中科院分区：
文献类型：
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作者：
Derijks, LJJ;Gilissen, LPL;Hooymans, PM
6-硫鸟嘌呤（6-TG）似乎是一个有吸引力的替代AZA和6-MP不耐受和耐IBD人群。然而，对IBD患者中6-TG的药代动力学、代谢物水平及其与药物疗效和毒性的相关性知之甚少。本研究报告了IBD患者人群中的6-TG药物代谢物浓度和代谢物浓度的预测价值。在t = 1时测量28名IBD患者的红细胞（RBC）6-硫代鸟嘌呤核苷酸（6-TGN）浓度。2. 4. 6-TG治疗8周后，20 mg，每日1次。结果指标包括平均6-TGN浓度（95%置信区间[C195%]）及其与TPMT基因型、6-TG剂量和8周期间血液学、肝脏、胰腺和疗效参数的相关性。4周后达到稳态6-TGN浓度，表明半衰期约为5天，测得856（C195%715 -997）pmol/8 × 108 RBC。在所有时间点均发生了较大的患者间变异性。未发现稳态6-TGN浓度与每千克体重药物剂量之间存在相关性。在有不良事件的患者和无任何事件的患者之间，6-TGNT浓度无显著差异。此外，平均6-TGN浓度在活动性疾病患者与缓解患者之间没有差异。在接受6-TG治疗的IBD患者中，代谢物浓度存在较大的个体间差异。在我们的人群中，我们不能证明6-TGN浓度与毒性和疗效之间存在明确的关系，如AZA和6-MP治疗的患者。
6-Thioguanine (6-TG) seems to be an attractive alternative in both AZA- and 6-MP-intolerant and -resistant IBD populations. However, little is known of 6-TG pharmacokinetics, metabolite levels, and their correlation with drug efficacy and toxicity in IBD patients. This study reports the 6-TG pharrnacokinetics in a Population of IBD patients and the predictive value of metabolite concentrations. Red blood cell (RBC) 6-thioguanine nucleotide (6-TGN) concentrations were measured in 28 IBD patients at t = 1. 2. 4. and 8 weeks after starting 6-TG, 20 mg once daily. Outcome measures included mean 6-TGN concentrations ( 95% confidence interval [C195%]) and their associations with TPMT genotype, 6-TG dose, and hematological, hepatic, pancreatic, and efficacy parameters during the 8 week period. Steady-state 6-TGN concentrations vere reached after 4 weeks, indicating a half-life of approximately 5 days, and measured 856 (C195% 715-997) pmol/8 X 108 RBCs. Large interpatient variability occurred at all time-points. No correlation was found between steady-state 6-TGN concentrations and drug dose per kilogram body weight. No significant differences in 6-TGNt concentrations were found between patients with adverse events and patients without any event. Also, mean 6-TGN concentrations did not differ in patients with active disease versus patients in remission. In IBD patients on 6-TG treatment, large interindividual differences in metabolite concentrations occur. In our population, we could not demonstrate a clear relationship between 6-TGN concentrations on one hand and toxicity and efficacy on the other, as exist in AZA- and 6-MP-treated patients.