Babiak L M, Cherry W F, Fayz S, Pang K S
Drug Metab Dispos. 1984 Nov-Dec;12(6):698-704.
Meperidine and normeperidine elimination was studied in the once-through perfused rat liver preparation. Biliary excretion of these bases was minimal, and nonlinear metabolism of meperidine (extraction ratio of 1.0 to 0.89 at 1 to 19 micrograms/ml) and normeperidine (extraction ratio of 0.6 to 0.1 at 1 to 25 micrograms/ml) was observed when input concentration was increased. The rate of efflux of normeperidine in hepatic venous blood represented an increasing proportion of the rate of presentation and the rate of loss of meperidine (34 to 92%) at increasing meperidine input concentration. But when the data were corrected for the nonlinear sequential metabolism of normeperidine, the rate of N-demethylation accounted completely for the rate of metabolism of meperidine. These N-demethylation rates obeyed Michaelis-Menten behavior, and appeared to be saturated at input meperidine concentration greater than 5 micrograms/ml.
在大鼠肝脏单次灌注制备中研究了哌替啶和去甲哌替啶的消除情况。这些碱的胆汁排泄极少，当输入浓度增加时，观察到哌替啶（浓度为1至19微克/毫升时提取率为1.0至0.89）和去甲哌替啶（浓度为1至25微克/毫升时提取率为0.6至0.1）的非线性代谢。随着哌替啶输入浓度增加，去甲哌替啶在肝静脉血中的流出率占呈现率和哌替啶损失率的比例不断增加（34%至92%）。但是，当对去甲哌替啶的非线性顺序代谢数据进行校正后，N-去甲基化率完全解释了哌替啶的代谢率。这些N-去甲基化率符合米氏动力学行为，并且在输入哌替啶浓度大于5微克/毫升时似乎达到饱和。
