Premedication medicines do not cause drug metabolic interaction with propofol using human liver microsomes in vitro.
OBJECTIVE
Propofol (2,6-diisopropylphenol) is widely used for anesthetic induction as well as for chronic sedation in intensive care units. In this study, we investigated the interaction between propofol and premedications, i.e., psychotropic and antianxiety agents (diazepam, midazolam), hypnotics (thiamylal), local anesthetics (lidocaine), depolarizing muscular relaxants (vecuronium), an antihypertensive (clonidine) and an H2-receptor antagonist (cimetidine) using human liver microsomes in vitro.


METHODS
The interaction effects between propofol and premedications were examined using human liver microsomal preparation in vitro. The concentration of propofol was determined by HPLC with UV detection.


RESULTS
The apparent Michaelis-Menten constant (Km) and the maximal velocity of total metabolic formation (Vmax) of propofol in human liver microsomes were 123 microM and 26.1 micromol/min per milligram of mg protein, respectively. Seven premedications (diazepam, midazolam, thiamylal, lidocaine, cimetidine, vecuronium, and clonidine) did not inhibit propofol metabolism in human liver microsomes at concentrations within the therapeutic range.


CONCLUSIONS
These results showed no interactions between propofol and seven premedication drugs within the therapeutic range of propofol using human liver microsomes in vitro.
Tanaka
Einosuke
E
Institute of Community Medicine, University of Tsukuba, 305-8575, Tsukuba-shi, Ibaraki-ken, Japan. einosuke@md.tsukuba.ac.jp
Takano
Yui
Y
Inomata
Shinichi
S
Toyooka
Hidenori
H
Honda
Katsuya
K
D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects*; D011229:Preanesthetic Medication; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D015742:Propofol