5-amino salicylic acid absorption and metabolism in ulcerative colitis patients receiving maintenance sulphasalazine, olsalazine or mesalazine.

BACKGROUND: All 5-aminosalicylic acid (5-ASA) preparations are potentially nephrotoxic, but there has been concern that newer delivery systems may increase this risk, either because of altered absorption or altered metabolism. Previous studies of 5-ASA absorption and excretion have usually either been performed in healthy controls or have only examined short-term therapy. 5-ASA and N-acetyl-5-ASA have therefore been measured in blood samples, and N-acetyl-5-ASA in urine samples, from patients with ulcerative colitis on long-term maintenance with different 5-ASA preparations and compared with sensitive markers of renal damage. METHODS: Patients receiving mesalazine (Asacol) (n = 13), sulphasalazine (n = 12) or olsalazine (Dipentum) (n = 8), all at doses within the recommended range were studied. Six-hour and trough serum concentrations of 5-ASA and N-acetyl-5-ASA and 24-h urinary excretion of N-acetyl-5-ASA were measured by high-performance liquid chromatography. RESULTS: Absorption of 5-ASA, assessed as 24-h excretion of N-acetyl-5-ASA expressed as molar % of ingested dose, was greater in patients receiving mesalazine, 23.25 +/- 10.65% (mean +/- s.d.; n = 13), than those receiving sulphasalazine (11.16 +/- 10.52%, n = 12; P = 0.003) or olsalazine (9.70 +/- 3.89%, n = 8; P < 0.002). The ratio of 5-ASA: N-acetyl-5-ASA in the serum 6 h after dose was also greater with mesalazine (1.02 +/- 0.44, mean +/- s.d.) than sulphasalazine (0.54 +/- 0.44, P < 0.02) or olsalazine (0.38 +/- 0.44, P < 0.005). Urinary markers of tubular damage were increased in four of 33 patients, but showed no correlation with concentration of 5-ASA or N-acetyl-5-ASA in serum and N-acetyl-5-ASA in urine, nor with lifetime dose or average daily dose of 5-ASA. CONCLUSIONS: In patients with ulcerative colitis receiving maintenance 5-ASA therapy there was greater absorption and less acetylation of 5-ASA from mesalazine (Asacol) compared with sulphasalazine or olsalazine, but no evidence from this study that this resulted in increased nephrotoxicity.

Oleuropein, an antioxidant polyphenol from olive oil, is poorly absorbed from isolated perfused rat intestine.

Epidemiological studies have shown that the incidence of heart disease and certain cancers is lower in the Mediterranean region. This has been attributed to the high consumption of olive oil in the Mediterranean diet, which contains polyphenolic compounds with antioxidant activity. Although many in vitro studies have been performed to elucidate mechanisms by which these compounds may act, there are virtually no data relating to their fate after ingestion. Therefore, we decided to investigate the intestinal absorption of one of the major olive oil polyphenolics, oleuropein. To do this, a novel in situ intestinal perfusion technique was developed, and the absorption of oleuropein was studied under both iso-osmotic and hypotonic luminal conditions. Oleuropein was absorbed, with an apparent permeability coefficient (P:(app)) of 1.47 +/- 0.13 x 10(-6) cm/s (+/-SE) observed under iso-osmotic conditions. The mechanism of absorption is unclear but may involve transcellular transport (SGLT1) or paracellular movement. Under hypotonic conditions, the permeability of oleuropein was significantly greater (5.92 +/- 0.49 x 10(-6) cm/s, P: < 0.001). This increase is thought to be due to an increase in paracellular movement facilitated by the opening of paracellular junctions in response to hypotonicity. Overall, we determined that the olive oil polyphenolic oleuropein can be absorbed, albeit poorly, from isolated perfused rat intestine. Therefore, it is possible that it or its metabolites may confer a positive health benefit after the consumption of olive oil, most likely via an antioxidant mechanism.

The in vivo fate of hydroxytyrosol and tyrosol, antioxidant phenolic constituents of olive oil, after intravenous and oral dosing of labeled compounds to rats.

In vitro studies have shown phenolics in olive oil to be strong radical scavengers. The absorption and elimination of two radiolabeled phenolic constituents of olive oil, hydroxytyrosol and tyrosol were studied in vivo using rats. Compounds were administered intravenously (in saline) and orally (in oil- and water-based solutions). For both compounds, the intravenously and orally administered oil-based dosings resulted in significantly greater elimination of the phenolics in urine within 24 h than the oral, aqueous dosing method. There was no significant difference in the amount of phenolic compounds eliminated in urine between the intravenous dosing method and the oral oil-based dosing method for either tyrosol or hydroxytyrosol. Oral bioavailability estimates of hydroxytyrosol when administered in an olive oil solution and when dosed as an aqueous solution were 99% and 75%, respectively. Oral bioavailability estimates of tyrosol, when orally administered in an olive oil solution and when dosed as an aqueous solution were 98% and 71%, respectively. This is the first study that has used a radiolabeled compound to study the in vivo biological fates of hydroxytyrosol and tyrosol.