Human UDP-glucuronosyltransferase (UGT) 2B10 in drug N-glucuronidation: substrate screening and comparison with UGT1A3 and UGT1A4.

摘要: Recent observations revealed that human UDP-glucuronosyltransferase (UGT) 2B10 catalyzes N-glucuronidation of amine-containing compounds. Knowledge the substrate specificity and clinical significance UGT2B10 is still limited. The purpose this study was to expand knowledge substrates evaluate its in drug clearance. Using recombinant UGT2B10, we found it amitriptyline, imipramine, ketotifen, pizotifen, olanzapine, diphenhydramine, tamoxifen, ketoconazole, midazolam. These are drugs were previously reported be for UGT1A4 or UGT1A3, contain their structure either tertiary aliphatic amines, cyclic an imidazole group. inactive glucuronidation desipramine, nortriptyline, carbamazepine, afloqualone. This group contains secondary primary these results suggest preferably conjugates amines. preference partial because did not conjugate amine trifluoperazine. Kinetic analyses affinity clearance diphenhydramine significantly higher than corresponding values although Vmax toward considerably higher. findings plays a major role at therapeutic concentrations. also supported by inhibition studies with nicotine hecogenin. In conclusion, expands understanding highlighting amines affinities those UGT1A3.