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Division of
Gastroenterology, Division of Clinical Pharmacology, Department of
Pharmacology, and Section of Biostatistics, Mayo Clinic, Rochester, MN,
USA
Correspondence to: Dr W J Sandborn, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. sandborn.william{at}mayo.edu
Accepted for publication 1 May 2001
AIM
We evaluated the
effect of coadministration of sulphasalazine, mesalamine, and
balsalazide on the pharmacokinetics and pharmacodynamics of
azathioprine and 6-mercaptopurine.
METHODSThirty four
patients with Crohn's disease receiving azathioprine or
6-mercaptopurine were enrolled in an eight week non-randomised parallel
group drug interaction study and 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 
3.5×109/l. Whole blood
6-thioguanine nucleotide concentrations were determined.
RESULTSThree 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.
CONCLUSIONSIn
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 and a high frequency of leucopenia.
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