Pharmacokinetics

Approximately 20-30% of orally administered sulfasalazine is absorbed in the small intestine. Much of this is taken up by the liver and excreted unmetabolized in the bile; the rest (~10%) is excreted unchanged in the urine. The remaining 70% reaches the colon, where, if cleaved completely by bacterial enzymes, it generates 400 mg mesalamine for every gram of the parent compound. Thereafter, the individual components of sulfasalazine follow different metabolic pathways. Sulfapyridine, which is highly lipid-soluble, is absorbed rapidly from the colon. It undergoes extensive hepatic metabolism, including acetylation and hydroxylation, conjugation with glucuronic acid, and excretion in the urine. The acetylation phenotype of the patient determines plasma levels of sulfapyridine and the probability of adverse effects; rapid acetylators have lower systemic levels of the drug and fewer adverse effects. By contrast, only 25% of mesalamine is absorbed from the colon, and most of the drug is excreted in the stool. Intraluminal concentrations of mesalamine therefore are very high (around 1500 mg/mL or 10 mM in patients taking a typical dose of 3 g/day).

The pH-sensitive coating of asacol (Eudagrit-S) limits gastric and small intestinal absorption of 5-ASA. The pharmacokinetics of pentasa differ somewhat. The ethylcellulose-coated microgranules are released in the upper GI tract as discrete, prolonged-release units of mesalamine. Acetylated mesalamine can be detected in the circulation within an hour after ingestion, indicating some rapid absorption, but some intact microgranules also can be detected in the colon. Because it is released in the small bowel, a greater fraction of pentasa is absorbed systemically compared with the other 5-ASA preparations.

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