Dasta J F, Weber R J, Wu L S, Sokoloski T D, Kakos G S, Smith D F, Howie M B
J Clin Pharmacol. 1986 Mar;26(3):165-8. doi: 10.1002/j.1552-4604.1986.tb02928.x.
The effect of cardiopulmonary bypass on the clearance of nitroglycerin (NTG) was studied in seven patients scheduled for coronary artery bypass graft surgery. Intravenous NTG was administered through nonadsorbing tubing at a starting dosage of 5-10 micrograms/min and was adjusted as needed. Blood samples were obtained from the radial artery and antecubital vein before bypass and from the arterial outlet of the oxygenator during bypass at least 30 minutes apart during a constant dosage or at least 30 minutes after a dosage change. Serum concentrations were analyzed for NTG by gas chromatography. Venous NTG concentrations were always lower than concurrent arterial concentrations, with an average arteriovenous extraction of 67.2%. Serum concentrations of NTG were generally within the range associated with a therapeutic response in congestive heart failure patients. Consistent with other reports, NTG concentrations varied widely among patients and considerable intrasubject fluctuations in drug concentrations were seen. The mean +/- SD apparent clearance of NTG before bypass of 0.044 +/- 0.02 L/kg/min increased 20% to 0.052 +/- 0.02 L/kg/min during bypass (P = .05). These results suggest that cardiopulmonary bypass increases the clearance of NTG; however, the magnitude appears to be small and only partially explains the reported increased dosage needed during cardiopulmonary bypass.
在七名计划进行冠状动脉搭桥手术的患者中,研究了体外循环对硝酸甘油(NTG)清除率的影响。静脉注射NTG通过无吸附性的管道给药,起始剂量为5-10微克/分钟,并根据需要进行调整。在体外循环前从桡动脉和肘前静脉采集血样,在体外循环期间从氧合器的动脉出口采集血样,在恒定剂量期间至少间隔30分钟,或在剂量改变后至少30分钟采集。通过气相色谱法分析血清中NTG的浓度。静脉NTG浓度始终低于同期动脉浓度,平均动静脉摄取率为67.2%。NTG的血清浓度一般在与充血性心力衰竭患者治疗反应相关的范围内。与其他报告一致,患者之间NTG浓度差异很大,并且观察到药物浓度在个体内有相当大的波动。体外循环前NTG的平均±标准差表观清除率为0.044±0.02升/千克/分钟,在体外循环期间增加20%至0.052±0.02升/千克/分钟(P = .05)。这些结果表明,体外循环增加了NTG的清除率;然而,增加幅度似乎较小,仅部分解释了体外循环期间所需剂量增加的报道。