Mechanism of Action of Apriso (Mesalamine)
Apriso (mesalamine) works primarily through topical anti-inflammatory effects on colonic epithelial cells by blocking cyclooxygenase and inhibiting prostaglandin production in the colon, thereby reducing inflammation in ulcerative colitis. 1
Pharmacological Mechanism
- Mesalamine's exact mechanism of action is not fully understood, but it appears to exert a local anti-inflammatory effect directly on the colonic mucosa 1
- It inhibits mucosal production of arachidonic acid metabolites through both cyclooxygenase and lipoxygenase pathways, which are increased in patients with ulcerative colitis 1
- Mesalamine blocks cyclooxygenase enzymes, resulting in decreased prostaglandin production in the colon, which helps reduce inflammation 1
Delivery System and Absorption
- Apriso consists of mesalamine granules in a polymer matrix with an enteric coating that dissolves at pH ≥6.0, targeting drug release to the mid-ileum and colon 2
- Each Apriso capsule contains 375mg of mesalamine in delayed-release granules 2
- The pH-dependent polymer coating ensures mesalamine is not released until it reaches the terminal ileum and colon, where the pH is higher, allowing for targeted delivery to inflamed areas 1
- Systemic absorption of mesalamine is limited (approximately 21-22% of administered dose), which helps minimize systemic side effects 1
Antimicrobial Properties
- Recent research has shown that mesalamine may also target bacterial polyphosphate accumulation, which sensitizes bacteria to oxidative stress 3
- This antimicrobial effect reduces bacterial colonization, attenuates persister cell formation, and diminishes biofilm development, potentially contributing to its therapeutic efficacy 3
Clinical Application
- Apriso is FDA-approved specifically for maintenance therapy in mild to moderate ulcerative colitis 2
- The once-daily dosing regimen (1.5g/day) improves medication adherence compared to other mesalamine formulations that require multiple daily doses 4, 5
- Clinical trials have shown that Apriso maintained remission in 79% of ulcerative colitis patients with high adherence rates (>90%) 4
Safety Considerations
- While generally well-tolerated, mesalamine can cause adverse effects including headache, nausea, and diarrhea 2
- Paradoxically, mesalamine can occasionally worsen diarrhea in some patients, which may be mistaken for worsening colitis 6
- Rare but serious idiosyncratic reactions include interstitial nephritis, which requires monitoring of renal function, especially in patients with pre-existing renal disease 1
- Very rare cases of mesalamine-induced cardiomyopathy and pneumonitis have been reported, highlighting the importance of monitoring for unusual symptoms 7
Dosing Considerations
- Apriso is typically administered as a once-daily dose of 1.5g (four 375mg capsules) 4
- Food intake increases systemic exposure to mesalamine (Cmax increased by 91%, AUC increased by 16%), so consistent administration with respect to meals is recommended 1
- Apriso is specifically approved for maintenance therapy, not for induction of remission in active disease 2