Dose loading with delayed‐release mesalazine: a study of tissue drug concentrations and standard pharmacokinetic parameters

Aims Tissue concentrations of 5‐aminosalicylic acid (5ASA) and its metabolites may influence the clinical course of inflammatory bowel disease. Since the factors that determine tissue drug concentrations are unknown we have studied the relationships between the oral dose of delayed‐release mesalazine, rectal tissue drug concentrations and standard pharmacokinetic parameters. Methods Twelve healthy volunteers were studied following 7 days treatment with 1.2, 2.4 and 4.8 g of delayed‐release mesalazine daily. 5‐aminosalicylic acid and N‐acetyl 5‐aminosalicylic acid concentrations were measured in serum, urine, stool and rectal tissue biopsies. Results Serum concentrations and 24 h urinary excretion of 5ASA and N‐acetyl 5ASA increased as the oral dose of mesalazine was increased from 1.2 g through 2.4 g to 4.8 g daily (serum area under curve (AUC):5ASA = 3.9, 15.4 and 46.8 µg ml−1 h, P