Sulphation of o-desmethylnaproxen and related compounds by human cytosolic sulfotransferases.

摘要: Naproxen is a nonsteroidal anti-inflammatory drug widely used as an analgesic and agent. The conjugated forms of naproxen O-DMN, its demethylated metabolite, account for 66-92% found in human urine. In this study, O-DMN structurally related compounds were tested substrates seven isoforms cytosolic sulfotransferase (SULT). SULT2 or hydroxysteroid SULT isoforms, SULT2A1 SULT2B1b, did not show reactivity with any the compounds. All five SULT1 active although there was variability between assayed. sulphated by SULT1A1, SULT1B1 SULT1E1. capable conjugating both alpha-naphthol beta-naphthol. Apparent Km values sulphation significantly higher than either SULTs 1A1, 1B1 1E1 had Kms 84 microM, 690 microM 341 respectively. These 40-1150-fold alpha- role side-chain studied using series beta-naphthol SULT1A1 presence lipophilic groups increased affinity whereas inclusion carboxyl group inhibited activity. studies indicate that B1 1E1. Because high concentrations expression liver intestines sulphation, may have first pass metabolism O-DMN.