DMD Celsis microsomes mean better data

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0090-9556/97/2503-0296-0300$02.00/0
DRUG METABOLISM AND DISPOSITION
Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics
Vol. 25, No. 3

Effect of Phenobarbital on the Pharmacokinetics of Lidocaine, Monoethylglycinexylidide and 3-Hydroxylidocaine in the Rat: Correlation with P450 Isoform Levels

Tatsuo Nakamoto, Yutaka Oda, Susumu Imaoka, Yoshihiko Funae, and Mitsugu Fujimori

Department of Anesthesiology and Intensive Care Medicine (T.N., Y.O., M.F.) and Laboratory of Chemistry (S.I., Y.F.), Osaka City University Medical School

To elucidate the effect of cytochrome P450 levels in hepatic microsomes on the metabolism of lidocaine in vivo, we investigated the metabolism of lidocaine in untreated (UT group) and phenobarbital-treated rats (PB group) in vivo and compared the results with those obtained by immunoblotting of rat hepatic microsomes. There were no differences in pharmacokinetic parameters for lidocaine between the UT and PB groups. The plasma concentrations of the N-deethylated metabolite of lidocaine, monoethyl-glycinexylidide (MEGX), in the PB group were significantly higher than those in the UT group. On the other hand, the plasma concentrations of the aromatic ring hydroxylated metabolite of lidocaine, 3-hydroxylidocaine (3-OH LID), were significantly lower in the PB group than in the UT group. When lidocaine metabolism was studied with hepatic microsomes prepared from rats in the UT and PB groups, the rates of formation of MEGX were higher in the microsomes of the PB group than in those of the UT group. The contents of CYP2B1 and 3A2 in rat hepatic microsomes of the PB group measured by immunoblotting were significantly higher than those of the UT group. Strong correlations were found between the area under the plasma concentration vs. time curve for MEGX and specific contents of CYP2B1 and 3A2. These findings suggest that formation of MEGX in vivo is dependent on the levels of CYP2B1 or 3A2 in rat liver.

Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics


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Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics.