Propofol decreases the clearance of midazolam by inhibiting CYP3A4: An in vivo and in vitro study

Abstract

Propofol decreases the clearance of midazolam, and the possible mechanism is the competitive inhibition of hepatic CYP3A4.

Propofol inhibits lidocaine metabolism in human and rat liver microsomes

“…It has recently been shown that lidocaine is metabolized by multiple hepatic CYP isoenzymes; CYP1A2 and 3A4 in humans [6], and 3A2 and 2B1 in the rats [10]. Propofol is also metabolized by 3A4 and 2B6 in humans [3,5] and by CYP1A2 and 2B1 in rats [2]. The rats possess CYP 3A2 as a homolog of 3A4 [9], instead of genuine 3A4 [11].…”

“…Drug metabolism generally occurs through hydroxylation and glucuronidation in the liver CYP system [3,4]. It was recently shown that the metabolism of propofol can be mediated by multiple hepatic CYP isoenzymes including CYP1A2 [2] and CYP3A4 [5]. The local anesthetic lidocaine can also be metabolized by CYP1A2 and CYP3A4 [6].…”

“…The local anesthetic lidocaine can also be metabolized by CYP1A2 and CYP3A4 [6]. Additionally, propofol has been shown to inhibit the metabolism of other drugs [5,7]. If a large dose of lidocaine is used for epidural anesthesia in combination with propofol for general anesthesia, local anesthetic toxicity and delayed emergence from anesthesia may result.…”

Toxicology of Specific Substances

“…It is well known that CYP3A4 inhibitors such as ketoconazole, ritonavir and others can significantly inhibit midazolam metabolism leading to a several hundred times longer half-life (Ahonen et al 1999;Hamaoka et al 1999;Oda et al 1999;Wang et al 1999Wang et al , 2000Kanazu et al 2005;Vossen et al 2007;Sugiyama et al 2011). The interand intraindividual expression of CYP3A4 is highly variable (as much as 40-fold) in humans (Wojnowski 2004).…”

Effect of propofol on ropivacaine metabolism in human liver microsomes

“…It was recently reported that propofol modified the activity of multiple hepatic CYP isozymes [1,2] including CYP1A2 [3] and CYP3A4 [4]. Additionally, propofol has been shown to inhibit the metabolism of such drugs [4,5].…”