Goldfrank L, Weisman R S, Errick J K, Lo M W
Ann Emerg Med. 1986 May;15(5):566-70. doi: 10.1016/s0196-0644(86)80994-5.
Naloxone hydrochloride is extremely valuable for diagnosing and managing the opioid overdose. Due to naloxone's short half life and a long duration of action of most opioids, repeated naloxone dosing often is required to prevent the recurrence of respiratory depression. An alternative to repeated bolus administration is a continuous IV infusion. We conducted a two-phase study to determine the pharmacokinetics of naloxone and to develop a continuous dosing nomogram. In the first phase seven patients were given an IV bolus dose alone and serial plasma naloxone levels were determined. Naloxone elimination was found to be biexponential with the mean beta half life equal to 0.023 +/- 0.002 reciprocal minutes in two patients and 0.015 +/- 0.02 reciprocal minutes in five patients. In the second phase ten volunteers were given either a 2-mg or a 4-mg bolus dose followed by a 1.5-mg/hr or a 3-mg/hr continuous infusion. The mean volume of distribution of the central compartment was found to be 0.806 +/- 0.408 L/kg. The mean beta rate constant of elimination was found to be 0.036 +/- 0.027 reciprocal minutes. A computer simulation of the pharmacokinetic parameters determined in our study found that a continuous infusion of two-thirds of the bolus dose that resulted in reversal each hour will maintain the plasma naloxone levels equal to or greater than the naloxone levels that would have existed 30 minutes following the bolus dose.
盐酸纳洛酮在诊断和处理阿片类药物过量方面极具价值。由于纳洛酮半衰期短，而大多数阿片类药物作用时间长，常常需要重复给予纳洛酮以防止呼吸抑制复发。重复推注给药的一种替代方法是静脉持续输注。我们进行了一项两阶段研究，以确定纳洛酮的药代动力学并制定持续给药剂量图。在第一阶段，仅对7名患者给予静脉推注剂量，并测定系列血浆纳洛酮水平。发现纳洛酮消除呈双指数，2名患者的平均β半衰期等于0.023±0.002分钟倒数，5名患者为0.015±0.02分钟倒数。在第二阶段，10名志愿者接受2毫克或4毫克推注剂量，随后分别以1.5毫克/小时或3毫克/小时持续输注。发现中央室的平均分布容积为0.806±0.408升/千克。发现平均β消除速率常数为0.036±0.027分钟倒数。对我们研究中确定的药代动力学参数进行计算机模拟发现，持续输注三分之二的推注剂量（每小时能导致逆转）将维持血浆纳洛酮水平等于或高于推注剂量后30分钟时本应存在的纳洛酮水平。
