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  • Title: [Effects of in vivo pretreatment with various barbiturates on lidocaine metabolism in rat liver microsomes].
    Author: Kakinohana M, Taira Y.
    Journal: Masui; 1994 Oct; 43(10):1534-40. PubMed ID: 7815706.
    Abstract:
    In male Wistar rats, we studied the effects of in vivo pretreatment with phenobarbital (PB), amobarbital (AB), hexobarbital (HB), pentobarbital (PT) or thiamylal (TI) on hepatic microsomal enzymes, and on deethylation of lidocaine in the microsomes. The rats of pretreatment groups received 0.1 ml of the above barbiturates (320 mumol.kg-1) and the control group received intramuscular injection of 0.9 % NaCl solution for 4 days. NADPH-cytochrome C reductase of the PB and AB groups increased significantly in activity and cytochrome b5 of only PB group increased in content. After the pretreatment with PB, TI produced higher microsomal cytochrome P-450 contents than in the control group. The potency of P-450 induction was in descending order of PB, TI, AB, HB and PT. Also we found the positive linear relationship between the potency of P-450 induction and the elimination half time (t1/2 beta) of the barbiturates. The activities of lidocaine deethylase with microsomes per P-450 of the pretreated rats with these five barbiturates (PB, AB, HB, PT and TI) were 2.4, 1.9, 2.2, 1.5 and 2.2 times of control values, respectively. Based on these results, we conclude that lidocaine deethylase activity of P-450 is increased by these five barbiturates whether levels of P-450 are increased quantitatively, or not.
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