Propofol inhibits enzymatic degradation of alfentanil and sufentanil by isolated liver microsomes in vitro.
We have studied the effect of propofol on the enzymatic degradation of alfentanil and sufentanil utilizing isolated liver microsomes obtained from pig and human liver. Propofol inhibited dose-dependently the oxidative metabolic degradation of alfentanil and sufentanil by both microsomal preparations. The calculated concentration of propofol causing 50% inhibition of metabolic degradation (IC50) was 32.6 mumol litre-1 for alfentanil and 22.1 mumol litre-1 for sufentanil in pig liver microsomes. Similar values of inhibitory activity of propofol (IC50 values 62.8 and 52.9 mumol litre-1, respectively) were observed using human microsomes prepared from liver taken from an organ transplant donor. We suggest that propofol in clinically relevant concentrations interferes with oxidative metabolic degradation of alfentanil and sufentanil in the microsomal fraction of pig and human liver.
Janicki
P K
PK
Department of Anaesthetics, University of Cape Town, Medical School, South Africa.
James
M F
MF
Erskine
W A
WA
D015760:Alfentanil / Q000378:metabolism*; D000777:Anesthetics / Q000378:metabolism*; D000818:Animals; D003864:Depression, Chemical; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*; D017409:Sufentanil; D013552:Swine
D000777:Anesthetics; D015760:Alfentanil; D017409:Sufentanil; D005283:Fentanyl; D015742:Propofol