| Interventions |
Pharmacokinetic Pilot Study Mesalazine (5-ASA) is an effective first-line therapy for patients with UC however there are no reports, positive or negative, of efficacy in PSC. 5-ASA is known to be rapidly N-acetylated once it is absorbed in the colon and released into the blood. N-acetylation inactivates 5-ASA, likely negating its effect before it reaches the biliary duct. Some 5-ASA escapes the intestine without being metabolized and is subsequently acetylated in the liver. The enzyme responsible for the N-acetylation is N- acetyltransferase 1, or NAT-1. NAT-1 is present in the lining of the intestine as well as in the liver. Quercetin is a flavonoid found in fruits and vegetables that has been shown to inhibit NAT-1. Quercetin was reviewed by the Food and Drug Administration (FDA) in 2010 and was given enerally recognised as safe(GRAS) designation at a dose of 1500mg/d. We propose that 5-ASA may be an effective therapy for primary sclerosing cholangitis (PSC). However, 5-ASA is metabolized to an inactive form preventing active 5-ASA to be able exert a therapeutic effect on the liver and biliary tree in PSC. Quercetin has been shown to inhibit N-acetyl transferase 1, the enzyme that metabolizes 5-ASA. Quercetin may also be therapeutic in PSC based on its anti-inflammatory properties. This pilot study aims to test if quercetin has a therapeutic potential in PSC by inhibiting NAT-1 and delivering active 5-ASA at a higher concentration to the liver. If successful, subsequent studies will examine its therapeutic potential in PSC. Participants already taking 5-ASA (4g daily, oral tablets or granules) will be enrolled. After the initial visit for screening and consent, participants will be instructed to continue their oral 5-ASA 4g tablets or granules, once a day in the morning before food. For baseline results without quercetin supplmentation, participants will return to the study centre on day 7 after continuing their prescribed |