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.