Enhanced bioavailability of azathioprine compared to 6-mercaptopurine therapy in inflammatory bowel disease: correlation with treatment efficacy

Background: Azathioprine and 6-mercaptopurine have proven efficacy in the t reatment of Crohn's disease. Immunosuppression is mediated by their intrace llular metabolism into active 6-thioguanine metabolites, and clinical respo nsiveness to therapy in patients with inflammatory bowel disease has been c orrelated with the measure of erythrocyte 6-thioguanine levels. Aims and methods: To perform a dosing equivalency analysis and comparison o f clinical efficacy in 82 patients with inflammatory bowel disease on long- term (> 2 months) therapy with either branded azathioprine (Imuran) (n = 26 ), generic azathioprine (n = 38), or 6-mercaptopurine (n = 18), based on th e measurement of erythrocyte 6-thioguanine metabolite levels, Results: Disease remission was achieved in 51% (42 out of 82) of patients t reated with either azathioprine or 6-mercaptopurine therapy, and correlated well with high erythrocyte 6-thioguanine levels (> 250 pmoles/ 8 x 10(8) R BCs), Patients treated with either branded azathioprine or 6-mercaptopurine achieved significantly higher erythrocyte 6-thioguanine levels than patien ts treated with generic azathioprine, thereby suggesting that branded azath ioprine has improved oral bioavailability compared to generic azathioprine. These data are consistent with the putative immunosuppressive role of 6-th ioguanine metabolites in the treatment of inflammatory bowel disease, and p rovides a basis for developing a therapeutic index of clinical efficacy bas ed on the measurement of erythrocyte 6-thioguanine metabolite levels. Conclusions: Our results suggest that differences in bioavailability may ha ve clinical relevance when considering the need to optimize erythrocyte 6-t hioguanine metabolite levels in patients deemed unresponsive to treatment o n conventional drug dosages.