Highly variable pH effects on the interaction of diclofenac and indomethacin with human UDP-glucuronosyltransferases

► Reaction pH strongly affects diclofenac and indomethacin glucuronidation. ► The pH effect is both enzyme dependent and substrate dependent. ► The reaction pH also affects the inhibition of UGT1A6 by NSAIDs. ► UGT2B15 is exceptionally sensitive to mildly acidic pH values. In vitro glucuronidation a...

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Veröffentlicht in:	Toxicology in vitro 2012-12, Vol.26 (8), p.1286-1293
Hauptverfasser:	Zhang, Hongbo, Soikkeli, Anne, Tolonen, Ari, Rousu, Timo, Hirvonen, Jouni, Finel, Moshe
Format:	Artikel
Sprache:	eng
Schlagworte:	Acyl migration Anti-Inflammatory Agents - administration & dosage Anti-Inflammatory Agents - metabolism Anti-Inflammatory Agents - pharmacology Diclofenac Diclofenac - administration & dosage Diclofenac - metabolism Diclofenac - pharmacology Glucuronides Glucuronosyltransferase - metabolism Humans Hydrogen-Ion Concentration Hymecromone - analogs & derivatives Hymecromone - metabolism Indomethacin Indomethacin - administration & dosage Indomethacin - metabolism Indomethacin - pharmacology Inhibitory Concentration 50 Naphthols - metabolism UDP-glucuronosyltransferase
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