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* = Presenting author

P533 Assessment of 6-thioguanine nucleotide metabolite level in inflammatory bowel disease patients treated with azathioprine

K. Pavlovska*1, M. Slaninka Miceska1, P. Mishevska2, J. Tonic Ribarska3, E. Atanasovska1, I. Kikerkov1, L. Efremovska4, M. Petrushevska1

1Medical faculty, Department of preclinical and clinical pharmacology and toxicology, Skopje, Macedonia, the former Yugoslav Republic of, 2Medical faculty, Gastroenterohepatology clinic, Skopje, Macedonia, the former Yugoslav Republic of, 3Faculty of pharmacy, Skopje, Macedonia, the former Yugoslav Republic of, 4Medical faculty, Institute of physiology, Skopje, Macedonia, the former Yugoslav Republic of

Background

Monitoring of 6-thioguanine nucleotide (6-TGN) level can be used to detect the risk of adverse events (AEs) in patients with inflammatory bowel disease (IBD) treated with azathioprine (AZA). The aims of this study were to assess the relationship between the 6-TGN metabolite level with the time duration of AZA therapy and azathioprine-related AEs in patients with IBD.

Methods

The concentration of 6-TGN metabolite level was determined using a high performance liquid chromatography (HPLC) method in 39 patients with IBD under AZA therapy more than 3 months. The AEs were determined and correlated with the level of 6-TGN. According to the 6-TGN level, patients were divided into 3 groups: sub-dosed group < 200 pmol/8 x 10(8) red blood cells (RBCs); therapeutic group 200–400 pmol/8 x 10(8) RBCs), and overdosed group > 400 pmol/8 x 10(8) RBCs).

Results

The average value of the 6-TGN level was 437.46 ± 198.82 pmol/8 x 10(8) RBCs (min: 64.8 pmol/8 x 10(8) RBCs; max: 905.5 RBCs).The average value of 6-TGN level in patients treated with AZA in a period of 3 to 12 months and more than 12 months was 460.06 ± 206.61 pmol/8 x 10(8) RBCs and 404.42 ± 189.99 pmol/8 x 10(8) RBCs, respectively, p > 0.05. When patients were analysed according to the 3 groups of 6-TGN level, the results have shown that from the patients under AZA therapy in a period of 3–12 months, 57.89% were considered overdosed; 31.58% were in the therapeutic group; and 10.53% were sub-dosed. In the group of patients who had used AZA more than 12 months, 61.54 % belonged to the therapeutic group, whereas 38.46% were overdosed. None of the patient was sub-dosed. Further, 9 patients where AZA-related AEs (33.33% alpha amylase increased; 22.22% elevated values of transaminases; 11.11% had leukocytopenia, aphthous ulcers, acute pancreatitis. and polyarthralgia, respectively) were observed had higher average value of the 6-TGN metabolite level when compared with those who did not have (487.54 ± 185.57 pmol/8 x 10(8) RBCs vs 429.11 ± 203.39 pmol/8 x 10(8) RBCs). In addition, 50% of the patients with AEs had average value of 6-TGN level of 562.8 pmol/8 x 10(8) RBCs compared with 50% of the group without AEs, where the average value level of 6-TGN was 399.5 pmol/8 x 10(8) RBCs. The majority of patients where AEs were observed belonged to the overdosed group (18.75%), followed by the therapeutic group with 14.29%. None of the patient from the sub-dosed group had AEs. In the overdosed group, all the patients that had AEs, had 6-TGN level above 450 pmol/8 x 10(8) RBCs.

Conclusion

Patients with higher 6-TGN level are at increased risk of azathioprine toxicity. Time duration of AZA therapy seems not to have any significant influence on 6-TGN metabolite level.