5 Glucuronidation and anaesthesia

Abstract

Glucuronidation is a major biotransformation reaction for xenobiotics, including the intravenous anaesthetic propofol and several analgesics. The UDP glucuronosyltransferases (UGTs) catalyse this reaction which requires UDP glucuronic acid (UDPGA) as its group-donating co-substrate. Each substrate is converted by one or several of the UGT enzyme forms. Therefore, competition for glucuronidation may occur for drugs; as yet there is little evidence that this plays an important role in the clinical situation. Volatile anaesthetics such as diethyl ether, halothane or the fluranes decrease the hepatic UDPGA concentration in animal experiments. Subsequently, glucuronidation of xenobiotics (and endobiotics such as bilirubin) may be decreased. Whether this plays a role in the patient is as yet unclear because data are lacking. In propofol elimination in man glucuronidation plays a dominant role: most of the dose is excreted in urine as propofol glucuronidation plays a dominant role: most of the dose is excreted in urine as propofol glucuronide or as a glucuronide of a secondary propofol metabolite. As yet no clear clinical interactions of propofol with other drug substrates for glucuronidation have been observed. Biological variation in glucuronidation due to, for instance, liver disease, drug interaction or genetic polymorphism in humans is reviewed.