5-氨基水杨酸对硫嘌呤类药物骨髓抑制的影响  

The impact of 5-aminosalicylic acid on bone marrow suppression caused by thiopurines

作　　者：高翔[1] 张芳宾[1] 杨荣萍[1] 肖英莲[1] 陈白莉[1] 陈旻湖[1] 胡品津[1] 

机构地区：[1]中山大学附属第一医院消化科,广州510080

出　　处：《中华消化杂志》2011年第8期550-554,共5页Chinese Journal of Digestion

基　　金：广东省自然科学基金（9151008901000181）

摘　　要：目的研究5-氨基水杨酸（5-ASA）对硫嘌呤类药物骨髓抑制的影响及其机制，探讨中国炎症性肠病（IBD）患者合用5-ASA时所需硫嘌呤类药物的剂量。方法回顾性分析服用硫嘌呤类药物IBD患者的临床资料，检测硫嘌呤甲基转移酶（TPMT）活性和红细胞6-硫鸟嘌呤核苷酸（6-TGN）浓度。前瞻性研究中先予患者硫唑嘌呤（AZA）50mg／d治疗4周，继而加用5-ASA3g／d治疗4周，检测第4、8周末红细胞6-TGN浓度。结果回顾性分析AzA／6-巯嘌呤（6-MP）＋5-ASA组45例、AZA／6-MP组94例患者，两组骨髓抑制发生率分别为46．7％和16．0％，多因素回归分析显示合用5-ASA为增加骨髓抑制的惟一独立危险因素（OR=3．45，95％CI：1．31～9．04）。TPMT活性在AZA／6-MP＋5ASA组和AzA／6-MP组之间差异无统计学意义（t=-0．351，P=0．734）。AZA／6-MP＋5-ASA组6-TGN浓度显著高于AZA／6一MP组（中位浓度为384．9pmol／8×10^8RBC比286．4pmol／8×10^8RBC，F：29．15，P=0．00）。8例患者完成前瞻性研究，予AZA50mg／d4周后，7例患者6-TGN浓度〈230pmol／8×10^8RBC;加用5-AsA4周后，7例患者6-TGN浓度≥230pmol／8×10^8RBC，其中3例6-TGN浓度≥420pmol／8×10^8RBC，2例发生骨髓抑制。结论当中国IBD患者合用5-ASA治疗时，采用常规推荐剂量的AZA／6-MP时骨髓抑制的发生概率增加，其机制可能与红细胞内6-TGN浓度升高有关，降低AZA剂量有可能在保持疗效的同时降低骨髓抑制发生率。Objective To evaluate the effect and mechanism of 5-aminosalicylic acid （5-ASA） on bone marrow suppression caused by thiopurines, and to explore the proper dosage of thiopurines when combined with 5-ASA for inflammatory bowel diseases （IBD） patients. Methods The clinical data of IBD patients who took thiopurines were retrospectively analyzed. Thiopurine methyltransferase （TPMT） activity and 6-thioguanine nucleotide （6-TGN） concentration were tested. In prospective study, patients firstly treated with azathioprine （AZA） of 50 mg/d for 4 weeks, then combined with 5- ASA of 3 g/d for another 4 weeks. The concentration of 6-TGN in red blood cells （RBC） was analyzed at the end of 4th and 8th week. Results In retrospective study, there were 45 cases in AZA/6-mercaptopurine （MP） combined with 5-ASA group, 94 patients were in AZA/6-MP alone group. The incidence of bone marrow suppression in these two groups were 46. 7% and 16. 0%, respectively. Multivariates regression analysis indicated co-administration of 5-ASA was the only risk factor of increasing bone marrow suppression incidence （OR = 3. 45,95% CI 1. 31 - 9. 04）. There was no significant difference of TPMT activity between AZA/6-MP combined with 5-ASA group and AZA/6- MP alone group（t=--0. 351 ,P=0. 734）. The 6-TGN concentration was significantly higher in AZA/ 6-MP combined with 5-ASA group than that of AZA/6-MP alone group （the median concentration was 384.9 pmol/ 8×10^8 RBCand286.4 pmol/ 8×10^8 RBC,F=29.15,P=0.00）. Prospective study was completed in 8 patients. After treated with AZA of 50 mg/d for 4 weeks, the 6-TGN concentration of 7 patients was lower than 230 pmol/8 ×10^8 RBC. After added with 5-ASA of 3 g/d for another 4 weeks, the 6-TGN concentration of 7 patients was over 230 pmol/8×10^8RBC, three patients of those was even higher than 420 pmol/8×10^8 RBC, and bone marrow suppression occurred in 2 patients. Conclusions The incidence of bone marrow suppression increased in Chinese IBD patients treated with reco

关 键 词：氨基水杨酸 硫唑嘌呤 6-巯嘌呤 骨髓疾病 剂量效应关系 药物 

分 类 号：R96[医药卫生—药理学]