COLAZIDE Capsule, hard Ref.[27543] Active ingredients: Balsalazide

Source: Medicines & Healthcare Products Regulatory Agency (GB)  Revision Year: 2018  Publisher: Almirall, S.A., Ronda General Mitre, 151, 08022 Barcelona, Spain

5.1. Pharmacodynamic properties

Pharmacotherapeutic group: Aminosalicylic and similar agents
ATC code: A07EC

Balsalazide consists of mesalazine linked to a carrier molecule (4-aminobenzoyl-ß-alanine) via an azo bond.

Bacterial azo-reduction releases mesalazine as an active metabolite in the colon. Mesalazine is an intestinal anti-inflammatory agent acting locally on the colonic mucosa. Its precise mechanism of action is unknown. Balsalazide and the carrier do not contribute to the pharmacodynamic action.

5.2. Pharmacokinetic properties

The pharmacokinetics of balsalazide and its metabolites have been studied in healthy subjects and patients in remission. The systemic uptake of balsalazide itself is low (<1%) and the major part of the dose is split in the colon by bacterial azoreductase. This cleavage results in the primary metabolites 5-aminosalicylic acid (5-ASA), responsible for the anti-inflammatory action, and 4-aminobenzoyl-beta-alanine (4-ABA), considered to be an inert carrier.

Most of the dose is eliminated via the faeces but about 25% of the released 5-ASA appears systemically predominantly as the N-acetylated metabolite (NASA) after inactivation in the colonic mucosa and liver. The systemic uptake of 4-ABA is only 10-15% of that of 5-ASA and also this metabolite is grossly N-acetylated (to NABA) in the first pass.

In urine, virtually only NASA and NABA are recovered and their renal clearances are high: 0.2-0.3 L/min and 0.4-0.5 L/min, respectively. The half-life of NASA is in the order of 6-9 hours. The half-life of 5-ASA itself is very short: about 1 hour.

Because of the great importance of renal clearance for the elimination, Colazide should be used with caution in renal impairment. No studies have been performed in patients with hepatic disease.

Protein binding of 5-ASA is about 40% and that of NASA about 80%. Available data suggest that the pharmacokinetics of balsalazide is not affected by genetic polymorphism, nor does age seem to be an important factor. Fasting slightly increases the systemic uptake of balsalazide and its metabolites.

5.3. Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional studies of genotoxicity, carcinogenic potential, toxicity to reproduction, safety pharmacology and validating kinetics and metabolism. In repeated dose toxicity studies, nephrotoxicity, an effect known to occur following mesalazine, was observed particularly in rats.

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