title: Effect of propofol on ropivacaine metabolism in human liver microsomes.
abstract: A combination of the general anesthetic propofol and epidural anesthesia with a local anesthetic is widely used. The metabolism of ropivacaine and that of lidocaine are mediated by similar P450 isoforms. Previously, propofol was found to inhibit the metabolism of lidocaine in vitro. Here we investigated whether propofol inhibits the metabolism of ropivacaine using human liver microsomes in vitro. Ropivacaine (6.0 micromol.l(-1)) as the substrate and propofol (1-100 micromol.l(-1)) were reacted together using human microsomes. The concentrations of ropivacaine and its major metabolite 2',6'-pipecoloxylidide (PPX) were measured using high-performance liquid chromatography. The metabolic activity of ropivacaine was reflected in the production of PPX. The inhibitory effects of propofol on ropivacaine metabolism were observed to be dose-dependent. The IC50 of propofol was 34.9 micromol.l(-1). Propofol shows a competitive inhibitory effect on the metabolism of ropivacaine (i.e., PPX production mediated by CYP3A4) in human CYP systems in vitro.
authors.affiliation: Graduate School, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Osaka
authors.forename: Shinichi
authors.initials: S
authors.lastname: Inomata
authors.forename: Einosuke
authors.initials: E
authors.lastname: Tanaka
authors.forename: Takako
authors.initials: T
authors.lastname: Nakamura
authors.forename: Katsuya
authors.initials: K
authors.lastname: Honda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyabe
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyooka
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000577:Amides / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004347:Drug Interactions; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*; D000077212:Ropivacaine
chemical_list: D000577:Amides; D065607:Cytochrome P-450 Enzyme Inhibitors; D000077212:Ropivacaine; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D015742:Propofol