The researchers evaluated the effect of coadministration of sulphasalazine, mesalamine, and balsalazide, in Crohn's disease patients, on the pharmacokinetics and pharmacodynamics of azathioprine and 6-mercaptopurine.
They reported their findings in the November issue of Gut.
A total of 34 Crohn's patients, receiving azathioprine or 6-mercaptopurine, were enrolled in an 8 week non-randomized drug interaction study. They were treated with mesalamine 4 g/day, sulphasalazine 4 g/day, or balsalazide 6.75 g/day.
The primary outcome measure was the occurrence of clinically important leucopenia during the study, defined separately as total leucocyte counts <3.0 x 109/l and 3.5 x 109/l.
Whole blood 6-thioguanine nucleotide concentrations were also determined.
| High prevalence of leucopenia in Crohn's patients who are coadministered drugs.
Some 3 patients could not be evaluated for the primary outcome measure.
In the remaining 31 patients, the frequency of total leucocyte counts <3.0 and 3.5 were: 1/10 and 5/10 in the mesalamine group; 1/11 and 6/11 in the sulphasalazine group; and 0/10 and 2/10 in the balsalazide group.
There were significant increases in mean whole blood 6-thioguanine nucleotide concentrations from baseline at most time points in the mesalamine and sulphasalazine groups, but not in the balsalazide group.
Author P. W. Lowry, of the Mayo Clinic, Rochester, Minnesota, concluded on behalf of fellow colleagues, "In patients with Crohn's disease receiving azathioprine or 6-mercaptopurine, coadministration of mesalamine, sulphasalazine, and possibly balsalazide, results in an increase in whole blood 6-thioguanine nucleotide concentrations. It also results in a high frequency of leucopenia."