Availability of Mesalazine (5-Aminosalicylic Acid) from Enemas and Suppositories during Steady-State Conditions

Abstract

The local and systemic bioavailability of a mesalazine enema (Pentasa®, Ferring A/S, Denmark) and a mesalazine suppository (Pentasa®, Ferring) was assessed during steady-state conditions. Eleven healthy subjects took 1 g of the enema or the suppository twice daily for 1 week, with a drug-free period of at least 1 week in between. At the end of each treatment period the urine and faeces were collected for 48 h, and the concentrations of mesalazine and the metabolite acetyl-mesalazine were measured. Plasma concentrations of drug and metabolite were measured hourly during a 12-h dose interval. The faecal water concentration of mesalazine was significantly higher after suppository treatment (55.7 mmol/1) compared with enema treatment (31.7 mmol/1) (p <0.01). The systemic absorption was low; 15% of daily mesalazine dose was recovered in urine after enema treatment and 10% after suppositores (p<0.01). Plasma concentrations were low, and no accumulation of either mesalazine or acetyl-mesalazine occurred. In conclusion, the enema and the suppository can be continuously administered as 1 g of mesalazine twice daily, respectively, giving high faecal water concentrations of mesalazine and a low systemic absorption.

Key Words:

• 5-Aminosalicylic acid
• enema
• mesalazine
• pharmacokinetics
• rectal administration
• suppository