What is known about the metabolism of balsalazide and Asacol?

Fråga: What is known about the metabolism of balsalazide and Asacol?

Sammanfattning: Balsalazide is a prodrug of mesalazine linked to 4-aminobenzoyl-alanine by an azo-bond and will be split off in the colon by bacterial azo-reductases.

Mesalzine is metabolised by the acetyltransferase, NAT1. Even if it is indicated that NAT1 is a structurally heterogenous gene there is no evidence for a genetic polymorphism of the rate of acetylation.

Svar: Balsalazide is a prodrug of mesalazine, 5-aminosalicylic acid (5-ASA) and not approved in Sweden (1). Balsalazide consists of mesalazine linked to 4-aminobenzoyl-alanine by an azo-bond and will be split off in the colon by bacterial azo-reductases thus leaving 5-ASA free to act in the colon (2). Asacol is one of the approved mesalazine products in Sweden (3). Mesalazine is ananti-inflammatory agent structurally related to the salicylates which are active in inflammatory bowel disease: it is considered to be the active moiety of sulphasalazine (4). Mesalazine is metabolised to N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) by N-acetylation in the intestinal epithelium and in the liver (5). According to results in studies it can be concluded that 5-ASA is metabolised by NAT1 and a systemic investigation of NAT1 variability in Caucasians indicates that NAT1 is encoded by a structurally heterogenous gene (7). The consequences of this heterogeneity for the activity of the enzyme is presently unknown.

In contrast to the care for sulphasalazine, the acetylation rate of 5-ASA is not bimodally distributed. Thus slow and fast acetylators of isoniazide do not differ with respect to plasma concentrations of 5-ASA and N-Ac-5-ASA, nor with respect to excretion patterns at steady-state (6).

Specifically, no correlation was found between isoniazid-sulfamethazine N-acetylation in vivo phenotype and the clearance of 5-ASA (7).