灌注猪肝中安替比林消除的米氏动力学

Michaëlis--Menten kinetics of phenazone elimination in the perfused pig liver.

作者信息

Andreasen B, Tonnesen K, Rabol A, Keiding S

出版信息

Acta Pharmacol Toxicol (Copenh). 1977 Jan;40(1):1-13. doi: 10.1111/j.1600-0773.1977.tb02048.x.

DOI:10.1111/j.1600-0773.1977.tb02048.x

Abstract

The purpose of the present study was to define the elimination kinetics of phenazone (NFN) in the isolated perfused pig liver. In five experiments phenazone was administered as constant infusion to obtain steady-state periods over a wide range of concentrations. The elimination of phenazone followed saturation kinetics (concentrations 0.1-12 mmol x 1(-1) and the maximal elimination rate (Vmax) was on average 102 mumol x min-1 x kg-1 liver and the Michaëlis-constant (Km) of 2.6 mmol x 1(-1). Estimates of Vmax and Km for the microsomal phenazone hydroxylase activity measured in liver biopsies found to be considerably lower than in the perfused liver. The hepatic elimination of phenazone during perfusion of pig liver at phenazone concentrations corresponding to human therapeutic doses follows first-order kinetics.

摘要

本研究的目的是确定非那宗（NFN）在离体灌注猪肝中的消除动力学。在五项实验中，非那宗以恒速输注的方式给药，以在广泛的浓度范围内获得稳态期。非那宗的消除遵循饱和动力学（浓度为0.1 - 12 mmol·L⁻¹），最大消除速率（Vmax）平均为102 μmol·min⁻¹·kg⁻¹肝脏，米氏常数（Km）为2.6 mmol·L⁻¹。在肝活检中测得的微粒体非那宗羟化酶活性的Vmax和Km估计值明显低于灌注肝脏中的值。在猪肝灌注过程中，对应于人类治疗剂量的非那宗浓度下，非那宗的肝脏消除遵循一级动力学。