Propofol inhibits lidocaine metabolism in human and rat liver microsomes

Abstract

Propofol possesses a dose-dependent inhibitory effect on the metabolism of lidocaine in both human and rat CYP systems in vitro.

Effect of propofol on ropivacaine metabolism in human liver microsomes

“…This suggests the possibility that metabolism of a drug going through CYP3A4 is restrained under anesthesia using propofol and ropivacaine in combination. The IC 50 of propofol in lidocaine metabolism in the previous study, 5.0 mg·ml -1 (28.0 mmol·l -1 ), is smaller than the present result [9]. With regard to this point, ropivacaine seems to be less inhibited by propofol than lidocaine is.…”

“…In a previous report, propofol metabolism was found not to be inhibited by some drugs used during general anesthesia [20]. In addition, whereas propofol inhibits lidocaine metabolism, propofol metabolism is not inhibited by lidocaine [9]. Considering these results, the affinity of propofol for CYP isoforms may be high compared with that of these drugs.…”

“…However, despite its relative innocuousness, ropivacaine does produce a toxic reaction [7]. In previous studies it was reported that lidocaine and ropivacaine are metabolized by CYP1A2 and CYP3A4 [8] and that propofol inhibits lidocaine metabolism in vitro [9]. On the other hand, the metabolic interaction of propofol and ropivacaine has not previously been reported.…”

“…Therefore, the CYP enzyme does not appear to play a major role in propofol metabolism compared to its role in that of other intravenously administered anesthetic drugs. The inhibitory effects of propofol on CYP isozymes [1,2] and the metabolism of drugs such as lidocaine [9] and midazolam [4] have been presented elsewhere. Midazolam is metabolized mainly by CYP3A4 and lidocaine mainly by CYP1A2 and CYP3A4.…”