Imunosupresivní terapie idiopatických střevních zánětů

• Main Author: Koubíková, Petra
• Other Authors: Lukáš, Milan
• Format: Doctoral Thesis
• Language: Czech
• Published: 2007
• Online Access: http://www.nusl.cz/ntk/nusl-288686

Background: Thioguanine derivatives, azathioprine (AZA) and 6-mercaptopurine (6-MP), have been used for many years in the treatment of inflammatory bowel disease (IBD). They represent major drugs in therapy of steroid-dependent and chronic active IBD. In 20-35% of the patients administration of AZA or 6-MP does not lead to improvement of the disease. Another limitation is the occurrence of adverse events of the therapy which can be observed in 10-15% of the patients. The metabolism of AZA/6-MP is influenced by thiopurine methyl transferase (TPMT). Since there is a significant variability in the activity of TPMP, there is an idea that monitoring the enzyme activity or the genotyping can significantly minimize the toxicity. Several studies have analysed correlation between the levels of AZA/6-MP and the efficacy or toxicity. The cut-off level corresponds to 230-250 pmol/8x108 RBC. High concentrations are linked with a risk of myelotoxicity. The occurrence of hepatotoxicity is dependent on the concentration of 6-methylmercaptopurine (6-MMP) in the erythrocytes. 6-thioguanine (6-TG) has been studied as an alternative therapy in patients with inflammatory bowel disease, who are resistant or intolerant to AZA/6-MP.The administration of 6-TG is effective in approximately 60% of patients. However, 6-TG...