[The inhibition of lidocaine metabolism by various barbiturates in rat hepatic microsome].
To evaluate the effects of various barbiturates on lidocaine metabolism by cytochrome P-450 (P-450), enzyme kinetics were analyzed in an in vitro study using rat hepatic microsomes. Phenobarbital, amobarbital, hexobarbital, pentobarbital, and thiamylal showed the mixed type inhibition of lidocaine metabolism with inhibition constants being 4.89, 1.08, 2.76, 0.77 and 0.65 mM, respectively. Same as lidocaine, all barbiturates used in the present study, corresponding to binding with P-450, induced the I type of spectral change of P-450. Since these did not affect cytochrome C reductase activity, it was suggested that this inhibition of lidocaine metabolism in hepatic microsomes may have been caused by the reduction of activity on P-450 by the barbiturates.
Kakinohana
M
M
Department of Anesthesiology, Faculty of Medicine, University of the Ryukyus, Okinawa.
Taira
Y
Y
Kakinohana
O
O
Okuda
Y
Y
D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D001463:Barbiturates / Q000494:pharmacology*; D002478:Cells, Cultured; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008012:Lidocaine / Q000493:pharmacokinetics*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D001463:Barbiturates; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D008012:Lidocaine