Steady-State Pharmacokinetics of a New 4-Gram 5-Aminosalicylic Acid Retention Enema in Patients with Ulcerative Colitis in Remission

Abstract

The pharmacokinetic profile of a new 4-g 5-aminosalicylic acid (5-ASA) retention enema, Mesasal®, was investigated. Nine patients with ulcerative colitis in remission and one patient with mild disease activity received one enema for seven consecutive nights. They were admitted to hospital for administration of the eighth enema. Plasma concentration and urinary excretion of 5-ASA and acetyl-5-aminosalicylic acid (Ac-5-ASA) were studied for 45 h and faecal excretion for 24 h after administration of the last enema. The median peak plasma concentration of 5-ASA was 0.92 (range, 0.59-1.87) μg/ml at a median of 11 h after administration, and of Ac-5-ASA 1.62 (range, 1.03-4.36) μg/ml at a median of 12 h after administration. On average, the plasma concentration of Ac-5-ASA was almost twice that of 5-ASA at each sampling period. At 24 h after administration the median plasma concentration for 5-ASA was 0.12 (range, 0-0.77) μg/ml and for Ac-5-ASA 0.36 (range, 0.01-1.6) μg/ml. At 45 h after administration low levels of both 5-ASA (<0.2 μg/ml) and Ac-5-ASA (>0.3 μg/ ml) were noted in two patients, low levels of only Ac-5-ASA (>0.1 μg/ml) in two patients, and neither 5-ASA nor Ac-5-ASA in the other six patients. All patients had detectable urinary levels of both 5-ASA and Ac-5-ASA during the first 4 h after administration. Median urinary recovery during 45 h was 12.6% (range, 5.6-22.2%), indicating a low absorption at steady-state conditions. Almost all of excreted 5-ASA (median, 87% range, 73-94%) was present as Ac-5-ASA. The median faecal recovery during 24 h was 29.4% (range, 8.1-75.3%). We found no evidence of accumulation of 5-ASA, which thus can be given safely at a dose of 4 g once daily.

Key Words:

• 5-Aminosalicylic acid
• enema
• mesalazine
• Mesasal®
• mezalamine
• pharmacokinetics
• ulcerative colitis