Parkar Suruchi P, Dherai Alpa J, Desai Devendra C, Ashavaid Tester F
Department of Laboratory Medicine, Division of Gastroenterology P. D. Hinduja Hospital and Medical Research Centre Mumbai India.
JGH Open. 2017 Sep 18;1(1):25-31. doi: 10.1002/jgh3.12004. eCollection 2017 Sep.
A lower dose requirement and higher toxicity of thiopurine is reported in Asian patients with inflammatory bowel disease (IBD) as compared with Caucasian patients. These reports are based on thiopurine methyltransferase measurement studies rather than metabolite estimation.We studied the utility of thiopurine metabolite estimation in Indian patients with IBD and compared dose and toxicity with Asian and Caucasian patients.
In this prospective study, 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine levels were determined by HPLC in 76 IBD patients treated with thiopurines. The levels were correlated with dose, disease activity, and toxicity. The dose-related metabolite levels and toxicity were compared with Caucasian and Asian patients reported in literature.
Of the 76 patients (32 women, mean age: 35.9 [SD: 14.54] years, 36 Crohn's disease and 40 ulcerative colitis), 1 non-compliant patient had undetectable level of metabolites. Of the 75 patients, 21(28%) had therapeutic level of 6-TGN, 37(49%) had subtherapeutic level and 17(23%) had supratherapeutic level. The 6-methylmercaptopurine levels ranged up to 4971 pmol/8 × 10 red blood cells. Six (8%) patients showed toxicity. Thiopurine dose was optimized in 20 (26.31%) patients. Dose-based metabolite levels were comparable to Asian and Caucasian patients. The toxicity (8%) observed in our patients was less than that reported (12-39%).
Half of the patients in this study had low and a quarter had high 6-TGN levels. One-fourth of the patients needed dose modification. The dose-based metabolite levels were comparable and the toxicity was less than that reported in Asian and Caucasian patients.
据报道，与白种人炎症性肠病（IBD）患者相比，亚洲IBD患者硫嘌呤的剂量需求较低，但毒性较高。这些报道基于硫嘌呤甲基转移酶测量研究，而非代谢物评估。我们研究了硫嘌呤代谢物评估在印度IBD患者中的实用性，并将剂量和毒性与亚洲及白种人患者进行比较。
在这项前瞻性研究中，通过高效液相色谱法测定了76例接受硫嘌呤治疗的IBD患者的6-硫鸟嘌呤核苷酸（6-TGN）和6-甲基巯基嘌呤水平。这些水平与剂量、疾病活动度和毒性相关。将剂量相关的代谢物水平和毒性与文献报道的白种人和亚洲患者进行比较。
76例患者（32例女性，平均年龄：35.9[标准差：14.54]岁，36例克罗恩病和40例溃疡性结肠炎）中，1例不依从患者的代谢物水平检测不到。75例患者中，21例（28%）的6-TGN水平处于治疗水平，37例（49%）处于亚治疗水平，17例（23%）处于超治疗水平。6-甲基巯基嘌呤水平最高达4971 pmol/8×10红细胞。6例（8%）患者出现毒性反应。20例（26.31%）患者的硫嘌呤剂量得到优化。基于剂量的代谢物水平与亚洲和白种人患者相当。我们患者中观察到的毒性（8%）低于报道的毒性（12%-39%）。
本研究中一半患者的6-TGN水平较低，四分之一患者的水平较高。四分之一的患者需要调整剂量。基于剂量的代谢物水平相当，且毒性低于亚洲和白种人患者报道的毒性。
