Pavlovska Kristina, Petrushevska Marija, Gjorgjievska Kalina, Zendelovska Dragica, Ribarska Jasmina Tonic, Kikerkov Igor, Gjatovska Liljana Labachevska, Atanasovska Emilija
Department of Preclinical and Clinical Pharmacology and Toxicology, Medical faculty, Skopje, Republic of Macedonia.
Faculty of Pharmacy, Skopje, R. Macedonia.
Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2019 May 1;40(1):73-79. doi: 10.2478/prilozi-2019-0006.
The active metabolite of azathioprine, 6-thioguanine nucleotide (6-TGN) is the main component responsible for the immunosuppressive effect in treatment of inflammatory bowel disease (IBD). The aim of this study was to assess the correlation between the concentration of 6-thioguanine nucleotide and disease activity, azathioprine-related adverse effects and time duration of treatment in patients with inflammatory bowel disease. Thirty-four patients were included in this study. Type of disease, gender, time duration of therapy and adverse effects were recorded. Metabolite concentration was determined by high performance liquid chromatography. Twenty-one percent of patients have experienced an adverse effect, with leucocytopenia most commonly occurring (42.9%). More adverse effects were registered when patients were treated with azathioprine in a period of less than 3 months in comparison to the group of patients that have been under therapy between 3-12 months and more than 12 months (p˂0.05). Most of the patients that presented any adverse effect had high 6-TGN concentration (>450 pmol/8x108 Er). The mean value of 6-TGN metabolite concentration in IBD patients treated with azathioprine was 437.46 pmol/8x108 Er ± 198.82 pmol/8x108. The time duration of azathioprine treatment did not have any significant impact on the achieved 6-TGN concentration (p>0.05).Twenty patients (58.9%) had achieved remission after therapy initiation with azathioprine. More alertness is recommended to clinicians towards patients in the first 3 months of the therapy. Our study demonstrated that higher 6-TGN concentration is associated with azathioprine toxicity.
硫唑嘌呤的活性代谢产物6-硫鸟嘌呤核苷酸(6-TGN)是治疗炎症性肠病(IBD)时发挥免疫抑制作用的主要成分。本研究旨在评估炎症性肠病患者体内6-硫鸟嘌呤核苷酸浓度与疾病活动度、硫唑嘌呤相关不良反应及治疗时长之间的相关性。本研究纳入了34例患者。记录疾病类型、性别、治疗时长及不良反应。采用高效液相色谱法测定代谢产物浓度。21%的患者出现了不良反应,其中白细胞减少最为常见(42.9%)。与治疗3至12个月及超过12个月的患者组相比,治疗时间少于3个月的患者使用硫唑嘌呤时出现的不良反应更多(p<0.05)。出现任何不良反应的大多数患者6-TGN浓度较高(>450 pmol/8×10⁸个红细胞)。接受硫唑嘌呤治疗的IBD患者中,6-TGN代谢产物浓度的平均值为437.46 pmol/8×10⁸个红细胞±198.82 pmol/8×10⁸个红细胞。硫唑嘌呤的治疗时长对所达到的6-TGN浓度没有任何显著影响(p>0.05)。20例患者(58.9%)在开始使用硫唑嘌呤治疗后实现了缓解。建议临床医生在治疗的前3个月对患者给予更多关注。我们的研究表明,较高的6-TGN浓度与硫唑嘌呤毒性相关。