Saville B A, Gray M R, Tam Y K
Drug Metab Dispos. 1987 Jan-Feb;15(1):17-21.
The steady state kinetics of lidocaine and its metabolites were modeled using nonlinear elimination pathways for multiple enzymes. The main metabolites, monoethylglycinexylidide and 3-hydroxy-lidocaine, were infused in the absence of lidocaine to measure the kinetic parameters for secondary elimination. Data from continuous perfusion of lidocaine in the isolated perfused rat liver at concentrations ranging from 9.6 to 278 microM (N = 16) were used to calculate the kinetic parameters for formation of the main metabolites. The elimination of lidocaine in the liver was approximated by the well stirred model. The whole liver study gave higher elimination rates than were predicted from microsomal studies. The major pathways for elimination of lidocaine in the rat were deethylation and hydroxylation, and subsequent elimination along these pathways accounted for the poor material balance at low dosage levels. The observed competitive inhibition of hydroxylation was in agreement with the predictions of the model.
利多卡因及其代谢物的稳态动力学采用多种酶的非线性消除途径进行建模。在无利多卡因的情况下输注主要代谢物单乙基甘氨酰二甲苯酰胺和3-羟基利多卡因，以测量二次消除的动力学参数。利用浓度范围为9.6至278微摩尔（N = 16）的利多卡因在离体灌注大鼠肝脏中连续灌注的数据，计算主要代谢物形成的动力学参数。肝脏中利多卡因的消除通过充分搅拌模型进行近似。全肝研究得出的消除率高于微粒体研究预测的消除率。大鼠体内利多卡因消除的主要途径是脱乙基化和羟基化，沿这些途径的后续消除导致低剂量水平下物质平衡不佳。观察到的羟基化竞争性抑制与模型预测一致。
