Kinetic Disposition and Hemodynamic Effects of Tetrandrine in Anesthetized Dogs
Kinetic Disposition and Hemodynamic Effects of Tetrandrine in Anesthetized Dogs
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粉防己碱对麻醉犬的动力学分布和血流动力学影响
DOI：
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发表时间：
1985
影响因子：
3
通讯作者：
R. Ogilvie
中科院分区：
文献类型：
--
作者：
F. Zeng;D. Shaw;R. Ogilvie
目的：研究粉防己碱13 mg/kg静注S以上对5只麻醉犬连续监测心电图和体动脉压的动态处置和血流动力学的影响。心输出量(CO)和肺毛细血管楔压(PCWP)的重复测定通过在肺动脉中的流动热稀释导管进行。每隔一段时间抽取血样，测定血浆粉防己碱或红细胞对药物的结合力。平均动脉压和舒张压在给药后5分钟内最大降幅为23±4%，而收缩压无明显变化。10min时CO最大上升52%，全身阻力下降51%，1~2 h逐渐恢复至基线水平，PCWP在5~10min出现一过性升高。PR间期略有延长，但R-R间期、QRS或QTc值无明显变化。MAP和PR间期的变化与粉防己碱血药浓度随时间的变化呈显著正相关，符合二室动力学模型，其分布t‘=7min，消除t’=88min。稳态时的表观分布体积为57 L/kg。血浆粉防己碱90%与血浆蛋白结合，˜44%全血粉防己碱与红细胞结合。粉防己碱是一种有效的动脉扩张药物，对麻醉犬的房室传导有轻微的影响，但没有明显的负性变力作用。
Summary: The kinetic disposition and hemodynamic effects of tetrandrine, 13 mg/kg i.v., over 30 s were studied in five anesthetized dogs during continuous monitoring of the ECG and systemic arterial pressure. Repeated determinations of cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were made via a flow-directed thermodilution catheter in the pulmonary artery. Blood samples were drawn at intervals for determination of plasma tetrandrine or erythrocyte binding of the drug. Maximal reductions in mean and diastolic arterial pressures of 23 ± 4% were observed within 5 min of the drug infusion without a change in systolic pressure. CO was increased maximally 52% and systemic resistance reduced 51% at 10 min, gradually returning to baseline values in 1–2 h. PCWP was increased transiently at 5–10 min. The PR interval was prolonged slightly without alteration in the R-R interval, QRS, or QTc. Changes in MAP and PR interval were correlated significantly with plasma tetrandrine concentrations over time, which followed a two-compartment kinetic model with a distribution t½ of 7 min and an elimination t½ of 88 min. The apparent volume of distribution at steady state was 57 L/kg. Plasma tetrandrine was >90% bound to plasma proteins, and ˜44% of whole blood tetrandrine was associated with erythrocytes. Tetrandrine is a potent arteriolar vasodilator drug with slight effects on AV conduction, but without significant negative inotropic effects in anesthetized dogs.