Once versus divided daily dosing with delayed-release mesalazine: a study of tissue drug concentrations and standard pharmacokinetic parameters

Background: Delayed-release mesalazine is traditionally taken as three divi ded doses. However, it is well-recognized that dosing frequency has a signi ficant impact on compliance and that once daily dosing is preferable. Methods: We measured serum, urinary, faecal and rectal tissue concentration s of 5-aminosalicylic acid and N-acetyl 5-aminosalicylic acid in 24 healthy volunteers following dosing with delayed-release mesalazine, 1.2 g or 2.4 g daily, given as either a single daily dose at 08:00 hours or in three div ided doses at 08:00, 13:00 and 18:00 hours. Results: Urinary and faecal excretion and rectal tissue concentrations of 5 -aminosalicylic acid and N-acetyl 5-aminosalicylic acid were similar follow ing single or divided daily dosing, at both doses studied. Peak serum conce ntrations were found at 06:00-09:00 following divided dosing and at 17:00-2 0:00 following once daily dosing. However, peak and trough serum levels and serum area under curve values (AUC) were similar with both regimens and at both doses. Conclusions: Urinary, faecal and rectal tissue concentrations are similar f ollowing single or divided daily dosing. Minor differences in serum levels were apparent but maximum, minimum and AUC values were similar. Clinical tr ials should examine the efficacy and toxicity of once daily dosing in patie nts with ulcerative colitis.