• Basic Info
• Clinical Info

Pharmacokinetics

Absorption

Bioavailability

Following oral administration of the 400-mg delayed-release tablets (Asacol^®), approximately 28% of mesalamine is absorbed and the remainder of the dose is available for topical activity and fecal excretion.

Following oral administration of extended-release capsules (Pentasa^®), about 20–30% of the drug is absorbed.

Following oral administration of the 1.2-g delayed-release tablets (Lialda^®), about 21–22% of the drug is absorbed.

Rectally administered suspension is poorly absorbed from the GI tract (about 15% [range: 5–35%]). The rectal suspension usually is retained for about 3.5–12 hours after administration as an enema; prolonged retention may increase absorption of the drug.

Variably absorbed following rectal administration of the suppositories. Rectal suppositories usually are retained for 1–3 hours after administration.

Food

Food does not appear to affect absorption of the 400-mg delayed-release tablets (Asacol^®).

Food decreases rate of absorption and increases extent of absorption of the 1.2-g delayed-release tablets (Lialda^®).

Distribution

Extent

Following oral or IV (IV preparation currently not available in the US) administration, the drug may be distributed into kidneys.

Rectal suspension distributes from the rectum into the colon, generally reaching the splenic flexure and possibly the ascending colon. Rectal suppositories distribute to some extent in rectal tissues.

Oral mesalamine crosses the placenta; serum concentrations of mesalamine in umbilical cord and amniotic fluid are very low.

Not known whether rectal mesalamine crosses the placenta.

Oral mesalamine is distributed into milk.

Not known whether rectal mesalamine is distributed into milk.

Plasma Protein Binding

Approximately 44–55% (as unchanged drug).

Approximately 43% at a concentration of 2.5 mcg/mL.

Elimination

Metabolism

Rapidly metabolized, principally in the liver to form N-acetyl-5-aminosalicylic acid.

Elimination Route

Following oral administration, excreted in urine (about 20%) mainly as metabolites and in feces.

Following rectal administration, principally excreted in feces (about 50%), as unchanged drug and metabolites, and in urine (about 10–35%).

Half-life

400-mg delayed-release tablets (Asacol^®): 12 hours (range: 2–15 hours).

1.2-g delayed-release tablets (Lialda^®): 7–9 hours (for mesalamine) and 8–12 hours (for N-acetyl-5-aminosalicylic acid metabolite).

Rectal suspension: 0.5–1.5 hours (for mesalamine) and 5–10 hours (for N-acetyl-5-aminosalicylic acid metabolite).

Rectal suppositories: 0.5–7 hours (for mesalamine) and 5–10 hours (for N-acetyl-5-aminosalicylic acid metabolite).

Stability

Storage

Oral

Extended-release Capsules

25°C (may be exposed to 15–30°C).

Delayed-release Tablets

400-mg tablets: 20–25°C.

1.2-g tablets: 15–25°C (may be exposed to 30°C).

Rectal

Suppositories

<25°C. Do not freeze; keep out of reach of children.

Suspension

20–25°C (may be exposed to 15–30°C); keep out of reach of children. May darken with time once the container has been removed from the foil wrap; dark brown suspensions should be discarded.

Actions

• Exerts local (rather than systemic) anti-inflammatory effects in the GI tract.
• May reduce inflammation in the colon by inhibiting cyclooxygenase and lipoxygenase, which catalyze the formation of prostaglandin precursors (endoperoxides) and of leukotrienes and hydroxyeicosatetraenoic acids, respectively, from arachidonic acid and/or its metabolites.