阿曲可林在心脏直视手术病人体内的药物动力学及药效学研究——体外循环前与体外循环中的比较

PHARMACOKINETICS AND PHARMACODYNAMICS OF ATRACURIUM BESYLATE IN PATIENTS BEFORE AND DURING CARDIOPULMONARY BYPASS——COMPARISON UNDER NORMAL TEMPERATURE AND UNDER LOW TEMPERATURE

本文研究了阿曲可林在心脏直视手术病人体内体外循环前及体外循环中的药物动力学和药效学性质,并进行比较。在对11例病人在体外循环前及体外循环中给药(0.5mg.kg^(-1))后的血药浓度及神经肌肉阻滞效应进行分析测定后,采用线性拟合求算出药物动力学参数值,以Sigmoid Emax模型拟合药效学参数。其体外循环前消除半衰期(t_(1/2)β)、分布半衰期(t_(1/2)α)、中央室分布容积(Vc)、血浆清除率(Cl)及药时曲线下面积(AUC)分别为19.67±0.37min、2.96±0.40min、50.36±9.08ml/kg、81.61±19.58ml/min和104.04±3.68μg/ml.min;体外循环中的t_(1/2)β、t_(1/2)α、Vc、Cl和AUC分别为25.20±1.45min、3.06±0.14min、53.01±6.09ml/kg、68.10±17.81ml/min和77.45±2.68μg/ml.min。其药效学参数:体外循环前的效应室消除速率常数(Keo)、实测最大效应值(Emax)、达最大效应50%时的药物浓度(CE_(50))及方程斜率(r)分别为0.1298±0.0658/min、95.56±6.17%、0.87±0.13μg/ml和4.01±1.35;体外循环中的药效学参数值分别为0.1313±0.0380/min、100%、0.16±0.10μg/ml和3.36±1.95。

Pharmacokinetics and pharmacodynamics of atracurium besylate in patients beforeand during cardiopulmonary bypass(CPB)was studied in 11 patients. Atracurium besylate was administeredintravenously 0.5 mg/kg. Before and during CPB, plasma atracurium concentrations of patients weremeasured by high-pressure liquid chromatography. Neuromuscular blockade effects were determined atthe adductor pollicis. after stimulation of the ulnar nerve. Pharmacokinetic parameters, the eliminationhalf-life(t1/2β), the distribution half-life(t1/2 a), the distribution volume of central compartment(Vc),plasma clearance (CL) and area under curve (AUC) were 19.67±3.37 min, 2.96±0.40 min, 50.36±9.08ml/kg,81.61±19.58 ml/min and 104.04±3.68 μg/ml. min before CPB, and 25.20±1.45 min, 3.06±0.14 min, 53.01±6.09 ml/kg. 68.10±17.81 ml/min and 77.45±2.68μg/ml. min during CPB, re-spectively. Pharmacodynamic parameters, rate constant of effect compartment(keo), measured makimum effect(Emax), concentration for 50% blockade (CE_(50)) and slope of the effect-concentration relationship(r)were 0.1298±0.0658 min, 95.62±6.08%, 0.87±0.13μg/ml and 4.01±1.35 before CPB, and 0.1313±0.0380 min, 100%, 0.16±0.10μg/ml and 3.36±1.95(n=9) during CPB, respectively. A SigmoidEmax Model was used to fit effect, measured as tl depression. The elimination half-life during CPB is longer than that before CPB. Neuromuscular blockade effectduring CPB is more rapid, stronger and lasted longer than that before CPB.