Article date: May 2002
By: L. J. J. Derijks, D. J. De Jong, L. P. L. Gilissen, L. G. J. B. Engels, C. J. J. Mulder, L. P. Bos, J. J. H. M. Lohman, P. M. Hooymans, in Volume 53, Issue 5, pages 546P-547P
Azathioprine (AZA) and 6‐mercaptopurine (6‐MP) are frequently used in the treatment of inflammatory bowel disease (IBD). However, about 10–20% of IBD‐patients are unable to tolerate AZA and/or 6‐MP due to side‐effects. 6‐Thioguanine (6‐TG), the active metabolite of AZA and 6‐MP, may be an alternative in these cases.
We measured 6‐TG levels in erythrocytes 4 weeks after start of 6‐TG therapy in nine out‐patients with IBD. 6‐TG concentrations were considered to reach steady state in 4 weeks having a half‐life of approximately 5 days. The mean age of the patients was 41 years (range 24–59), three were male, six were female. Two patients were intolerant to 6‐MP, 5 to AZA and two to both drugs. Five patients received a daily dose of 20 mg, four were given 40 mg. The results are summarized in Table 1.
* 6‐TG concentrations at t=4 weeks, at t=2 weeks (
#) and at t=1 week (
##) in pmol/8×108 RBC.
UC=ulcerative colitis, CD=Crohn's disease.
Poor correlation was found between dose and 6‐TG concentration (r : 0.34). 6‐TG concentrations after 6‐TG intake are relatively high compared with blood concentrations measured in AZA or 6‐MP treated patients (mean: 276, range: 0–792) [1]. Beside drug efficacy 6‐TG concentrations are also associated with bone marrow suppression, especially when these concentrations are high; Dubinsky et al. [1] measured a mean 6‐TG concentration of 490 in a pediatric leukopenic population treated with AZA or 6‐MP [2].
No leukopenia was observed in our 6‐TG treated group.
One of our patients showed an early allergic reaction to 6‐TG and developed high fever and erythema nodosum within the first week (patient 2). Another patient discontinued 6‐TG after 3 weeks because of total malaise (patient 1). Late, pharmacological explainable adverse reactions due to high 6‐TG concentrations did not occur in the 4 week period.
These results suggest that 6‐TG may serve as a safe alternative in AZA and 6‐MP intolerant IBD‐patients. Frequent 6‐TG concentration measurement and leukocyte counts are mandatory in determining optimal dose and guaranteeing safety. Further data are needed to establish safety and efficacy in the long term. We therefore initiated a prospective multicenter clinical trial.
DOI: 10.1046/j.1365-2125.2002.16137.x
View this article