Drug-Drug Interaction between Anaesthetic Drug Propofol and Andrographolide Derivative

Drug-drug interaction was speculated and investigated between andrographolide derivative and propofol, which is an important anaesthetic drug. The in vitro incubation system for propofol glucuronidation was used, and both recombinant UGT1A9 and human liver microsomes (HLMs) were selected as enzyme sources; 100 mu M of andrographolide derivative (AD) strongly inhibited the glucuronidation of propofol catalyzed by recombinant UGT1A9 and 100 mu M of andrographolide derivative (AD) also strongly inhibited the glucuronidation of propofol catalyzed by human liver microsomes (HLMs). Lineweaver-Burk plot indicated that AD competitively inhibited the glucuronidation of propofol catalyzed by recombinant UGT1A9 and human liver microsomes (HLMs). The fitting equation was y = 9.2x + 188 and y = 7.2x + 211.7 for the inhibition of AD towards glucuronidation of propofol catalyzed by recombinant UGT1A9 and human liver microsomes (HLMs), respectively. Using these equations, the inhibition kinetic parameters (K-i) were 20.0 and 29.4 mu M for the inhibition of AD towards glucuronidation of propofol catalyzed by recombinant UGT1A9 and human liver microsomes. In conclusion, an important andrographolide derivative was synthesized in this study, and its inhibition capability towards UGT1A9-catalyzed propofol glucuronidation was demonstrated in the incubation system with recombinant UGT1A9 and human liver microsomes (HLMs) as enzyme source.