Similar Pharmacokinetics of Three Dosing Regimens Comprising Two Oral Delayed-Release Mesalamine Formulations in Healthy Adult Volunteers: Randomised, Open-Label, Parallel-Group Study.

AIMS: Mesalamine is the first-line therapy for treating mild-to-moderate ulcerative colitis. Multiple mesalamine formulations are available, with similar safety and efficacy profiles. Mesalamine is commonly administered as divided dosing, although once-daily dosing may provide benefits for patients. We evaluated pharmacokinetics of three dosing regimens of two oral delayed-release mesalamine formulations in healthy adult volunteers.

METHODS: Randomised, open-label, parallel-group study of mesalamine pharmacokinetics following Lialda 2× 1.2 g once-daily [QD] (Dose A), Asacol 6× 400 mg QD [Dose B], or Asacol 2× 400 mg three-times-daily [TID] (Dose C), over 7 days. Assessments included 5-aminosalicylic acid [5-ASA] and N-acetyl 5-aminosalicylic acid [N-Ac-5-ASA; primary metabolite] pharmacokinetics [Ae (%), AUC0-24 and Cmax ], safety and tolerability.

RESULTS: All enrolled volunteers [N = 37] completed the study. Steady-state was achieved for all treatments by Day 4. Ratios (95% CI) of means for steady-state AUC0-24 [Dose A vs B: 90.3% (39.8, 204.8); Dose A vs C: 123.5% (55.3, 275.7); Dose B vs C: 136.8% (61.3, 305.5)] and Cmax [Dose A vs B: 106.0% (46.4, 242.2); Dose A vs C: 133.0% [59.1, 299.0]; Dose B vs C: 125.5% (55.8, 282.1)] were similar for all 5-ASA treatments. Mean urinary excretion of 5-ASA plus N-Ac-5-ASA was comparable between treatments [Dose A: 21.3%; Dose B: 20.2%; Dose C: 17.9%]. All treatment regimens were well tolerated; no safety issues were observed.

CONCLUSIONS: Plasma and urine pharmacokinetics for Asacol TID, Asacol QD and Lialda QD are similar, suggesting similar daily systemic exposures can be obtained with either TID or QD dosing. NCT00751699.