Wright, S.; Sanders, D.S.; Lennard, L.; Lobo, A.J.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA13
Academic Journal
Introduction: Azathioprine is well established in the treatment of inflammatory bowel disease (IBD). Thioguanine nucleotides (TGNs) are active azathioprine metabolites, elevated TGNs are associated with myelosuppression. Aim: To investigate TGN metabolite concentrations in a large cohort of IBD patients. MethBD patients on constant dose azathioprine were studied over a 2 year period. Blood samples (10 mL) were taken for the monitoring of blood counts and the measurement of red cell (RBC) TGN metabolite concentrations at each clinic visit. Results: 159 patients (88 men, 71 women) were recruited into the study. 156 had multiple metabolite assays. In 111 patients (3 to 14 assays, median 6) TGN concentrations varied by < 50%, this group was defined as steady-state. 104 patients remained in remission, 7 developed active disease. Twenty patients (13%) on constant azathioprine dosage showed evidence of non-compliance (eg nil metabolites). Twenty-five had dosage adjustments, 20 due to active IBD, 1 with concurrent rheumatoid arthritis and 4 dose reductions (2 in prolonged IBD remission, 2 with neutropenia). TGN concentrations in the n = 104 steady state group ranged from 70 to 717 pmol/8×10[sup 8] RBCs (median 236) compared with 70 to 517 (median 175) in the 27 IBD patients with active disease (median difference between remission and active disease = 44 pmol, p <0.05). The two neutropenic patients (azathioprine 1.96 and 1.78×10[sup 9]/L) had TGN concentrations of 452 and 376 pmol. The azathioprine dose for the 104 patients in remission ranged from 0.4 to 2.8 mg/kg (median 1.8), no different from that in those with active disease (0.6 to 2.5 mg/kg). There was no correlation between azathioprine dose and TGN concentrations (r[sub s]=0.2). Conclusion: IBD patients with active disease have significantly lower TGN concentrations than those patients in remission.


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