Stereoselective Glucuronidation of Propafenone and Its Analogues by Human Recombinant UGT1A9

概要

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Stereoselective glucuronidation of propafenone and its β-blocker analogues by human recombinant UGT1A3 and UGT1A9 from the recombinant baculovirus in insect sf9 cells was studied. The glucuronides produced in incubation mixtures were assayed by HPLC equipped with UV detector, and identified by β-glucuronidase. The stereoselective glucuronidation was measured by pre-column 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocynate (GITC) derivatization HPLC method for propafenone and esomolol. In all of ten β-blocker drugs studied, six showed the glucuronidation activity with UGT1A9, while four with UGT1A3. From roughly quantitative stereoselective glucuronidation study of racemic β-blocker analogues by UGT1A9, propranolol had a high ratio of the ratios of S- to R-isomer glucuronide (S-G/R-G), about 4.3, the ratios of terbutaline, atenolol and esomolol were 3.3, 3.1 and 2.8 respectively, sotalol and propafenone were 2.3 and 2.0. In a word, S-isomers of these drugs were glucuronidated by human UGT1A9 much faster than their antipodes.
公益社団法人　日本薬学会の論文