Mesalazine release from a pH dependent formulation: effects of omeprazole and lactulose co-administration

Abstract

Aims: Delayed-release formulations of mesalazine often rely on the gastrointestinal luminal pH profile to deliver 5-aminosalicylic acid (5ASA) to the colon. The aim of this study was to examine the influence of luminal pH on mesalazine release.

Methods: We studied the effect of co-administration of omeprazole and lactulose on the steady-state pharmacokinetics of Eudragit S-coated mesalazine in healthy volunteers.

Results: No significant changes in urinary or faecal levels of 5ASA or its main metabolite, N-acetyl 5ASA, were apparent.

Conclusions: This study suggests that co-administration of omeprazole and lactulose does not impair the release of delayed-release mesalazine.

Figure 1

24 h urinary and faecal excretion (mean±s.e.mean) of 5-aminosalicylic acid (5ASA, □) and N-acetyl-5-aminosalicylic acid (NA5ASA, ▪) following administration of omeprazole. Repeated measures ANOVA: 24 h urinary excretion-5ASA P=0.6 (95% CI 13 to −11 mg), NA5ASA P=0.3 (95% CI 30 to −144 mg); 24 h faecal excretion-5ASA P=0.3 (95% CI 28 to −178 mg), NA5ASA P=0.2 (95% CI 147 to −72 mg).

Figure 2

24 h urinary and faecal excretion (mean±s.e.mean) of 5-aminosalicylic acid (5ASA, □) and N-acetyl-5-aminosalicylic acid (NA5ASA, ▪) following administration of lactulose. Repeated measures ANOVA: 24 h urinary excretion-5ASA P=1.0 (95% CI 28 to −34 mg), NA5ASA P=0.4 (95% CI 62 to −187 mg); 24 h faecal excretion-5ASA P=0.3 (95% CI 68 to −240 mg), NA5ASA P=0.7 (95% CI 199 to −252 mg).