PHARMACOKINETICS OF REMIFENTANIL (GI87084B) AND ITS MAJOR METABOLITE (GI90291) IN PATIENTS UNDERGOING ELECTIVE INPATIENT SURGERY
PHARMACOKINETICS OF REMIFENTANIL (GI87084B) AND ITS MAJOR METABOLITE (GI90291) IN PATIENTS UNDERGOING ELECTIVE INPATIENT SURGERY
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DOI：
10.1097/00000542-199311000-00005
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发表时间：
1993-11-01
期刊：
影响因子：
8.8
通讯作者：
MUIR, KT
中科院分区：
文献类型：
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作者：
WESTMORELAND, CL;HOKE, JF;MUIR, KT
背景瑞芬太尼是一种高效阿片类药物，由于其在血液和组织中被酯酶快速水解，起效迅速，作用持续时间短。方法：对24例择期手术患者进行瑞芬太尼及其主要代谢产物G190291的药代动力学研究。瑞芬太尼在麻醉诱导和气管插管后1分钟输注（2、5、15和30 μ g/kg）。结果：瑞芬太尼和G190291在大鼠体内的药代动力学符合三室模型。瑞芬太尼的总清除率（250-300 l/h）与剂量无关，约为正常肝血流量的3 - 4倍。稳态分布容积（25-40 1）也与剂量无关。瑞芬太尼的终末半衰期范围为10至21分钟。瑞芬太尼清除率和患者人口统计学的协变量分析显示，患者体重、年龄和性别不影响总清除率。这表明瑞芬太尼可能不需要根据成年患者的体重给药。进行模拟以确定在设计用于维持恒定效应部位浓度的输注后效应部位浓度降低50%所需的时间。瑞芬太尼效应室浓度降低50%所需的时间（3.65 min）明显少于舒芬太尼（33.9 min）、阿芬太尼（58.5 min）和芬太尼（262 min）。主要代谢产物GI 90291的药代动力学与瑞芬太尼剂量无关。G190291的平均终末半衰期范围为88至137分钟。结论：瑞芬太尼的药代动力学与其快速消除血液和组织酯酶是一致的，其主要代谢产物消除更慢，但不太可能作出任何显着的贡献，因为其效力低得多的总效果。瑞芬太尼起效快，作用持续时间短，因此非常适合剂量滴定（输注速率），以达到预期的效果。
Background. Remifentanil is a highly potent opioid with a rapid onset and a short duration of action due to its rapid hydrolysis by esterases in blood and tissues. The major metabolite of remifentanil, GI90291, is much less potent than remifentanil.Methods: The pharmacokinetics of remifentanil and its major metabolite, G190291, were determined in 24 patients undergoing elective inpatient surgery. Remifentanil was administered as a 1-min infusion (2, 5, 15, and 30 mug/kg) after the induction of anesthesia and tracheal intubation. Serial arterial blood samples were collected over 6 h and assayed for remifentanil and G190291.Results: The pharmacokinetics of remifentanil were described using a three-compartment model. Total clearance (250-300 1/h) of remifentanil was independent of dose and was approximately three to four times greater than the normal hepatic blood flow. Volume of distribution at steady state (25-40 1) also was independent of dose. The terminal half-life of remifentanil ranged from 10 to 21 min. Covariate analysis of remifentanil clearance and patient demographics showed that patient body weight, age, and gender did not influence total clearance. This suggests that remifentanil may not need to be dosed according to body weight in adult patients. A simulation was conducted to determine the time required for a 50% reduction in effect site concentration after an infusion designed to maintain a constant effect site concentration. The time required for a 50% reduction in the effect site concentration of remifentanil (3.65 min) was considerably less than that for sufentanil (33.9 min), alfentanil (58.5 min), and fentanyl (262 min). The pharmacokinetics of the major metabolite, GI90291, were independent of the dose of remifentanil. The mean terminal half-life of G190291 ranged from 88 to 137 min.Conclusions: The pharmacokinetics of remifentanil are consistent with its rapid elimination by blood and tissue esterases; its major metabolite is eliminated more slowly but is not likely to make any significant contribution to the total effect because of its much lower potency. The rapid onset and short duration of action of remifentanil make it well suited for titration of dose (infusion rate) to the desired degree of effect.