Characterization of Bucolome N-Glucuronide Formation: Tissue Specificity and Identification of Rat UDP-Glucuronosyltransferase Isoform (s)

Bucolome N-glucuronide (BCP-NG, main metabolite of bucolome (BCP) is the first N-glucuronide of barbituric acid derivatives isolated from rat bile. The objective of this study was to identify the main tissue producing BCP-NG and the molecular species of BCP-NG-producing UGT. Four target tissues were investigated: the liver, small and large intestines, and kidney. To identify the UGT molecular species responsible for BCP-NG formation, yeast microsomes expressing each rat UGT isoform were prepared. BCP-NG formation was detected in all microsomal fractions of the 4 tissues. The liver microsomal BCP-NG-producing activity was the highest, followed by that in the small intestinal microsomes, showing about 41% of the liver microsomal activity level. BCP-NG-producing activity (min-1) was determined in yeast microsomal fractions expressing rat UGT isoforms, and the activity was detected in UGT1A1 (0.059), UGT1A2 (0.318), UGT1A3 (0.001), UGT1A7 (0.003), UGT2B1 (0.004), UGT2B3 (0.091), and UGT2B6 (0.031), showing particularly high levels for UGT1A1 and UGT1A2 among the UGT1A isoforms. It was clarified that UGT1A1, widely distributed in rat tissues, is the molecular species responsible for BCP-NG formation.

Analysis of Adverse Drug Reactions Caused by Chinese Patent Medicine Treatment Based on Kidney Damp-heat Syndrome and Damp-turbidity Syndrome

[Objectives]To determine relationship of the adverse drug reaction(ADR)occurrence of the single use and combined use of Huangkui Capsule and Haikun Shenxi Capsule.[Methods]To determine relationship of the ADR occurrence of the single use and combined use of Huangkui Capsule and Haikun Shenxi Capsule.[Results]The main adverse drug reactions of the single use of Huangkui Capsule or Haikun Shenxi Capsule was severe diarrhea(n=7,n=9),however the combined use of the two resulted in more occurrence of adverse drug reactions(n=23)with significant difference in contrast to the single use group(P=0.0015,P=0.0069).[Conclusions]When traditional Chinese patent medicines are used in combination to treat kidney damp-heat syndrome and damp-turbid syndrome,it is necessary to pay close attention to the occurrence of adverse drug reactions,especially the digestive system.