Choi Byung-Moon, Lee Yong-Hun, An Sang-Mee, Lee Soo-Han, Lee Eun-Kyung, Noh Gyu-Jeong
Department of Anesthesiology and Pain Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Division of Drug Safety Evaluation New Drug Development Center, Osong Medical Innovation Foundation, Chungju-si, Chungbuk, Republic of Korea.
Br J Clin Pharmacol. 2017 Feb;83(2):314-325. doi: 10.1111/bcp.13101. Epub 2016 Sep 29.
This prospective study aimed to characterize the population pharmacokinetics of intravenous oxycodone and to determine the minimum effective concentration (MEC) and minimum effective analgesic concentration (MEAC) of oxycodone for major open intra-abdominal surgery.
In the pharmacokinetic study, patients were administered intravenous oxycodone (0.1 mg kg ), and arterial blood was sampled at pre-set intervals. In the analgesic-potency study, patients were administered intravenous oxycodone (0.1 mg kg ) 30 min before the end of the surgery, were placed in the postoperative anaesthesia care unit (PACU), and were asked to rate their pain every 10 min using a visual analogue scale (0 = no pain, 10 = most severe pain). On the first occasion that wound pain at rest and during compression was rated as ≥3 or ≥5, respectively, the first blood sample was obtained to determine the MEC. A second blood sample was obtained after titration with 2 mg of oxycodone to yield wound pain <3 at rest and <5 during wound compression, and MEAC was determined. MEC and MEAC were determined again in each patient.
In the population pharmacokinetic study (n = 54), oxycodone plasma concentration over time was well described by a three-compartment mammillary model. Lean body mass and age were significant covariates for the volume of distribution and metabolic clearance of the pharmacokinetic model of oxycodone, respectively. The analgesic-potency study (n = 50) showed that the median (95% CI) MEC and MEAC were 31.5 (19.2-42.8) and 74.1 (29.2-128.3) ng ml (first measurements) and 63.4 (15.6-120.1) and 76.1 (32.9-132.7) ng ml (second measurements), respectively.
In major intra-abdominal open surgery, the MEAC and analgesic potency of oxycodone were 75 ng ml and 60 ng ml , respectively.
本前瞻性研究旨在描述静脉注射羟考酮的群体药代动力学特征，并确定腹部开放性大手术中羟考酮的最低有效浓度（MEC）和最低有效镇痛浓度（MEAC）。
在药代动力学研究中，给患者静脉注射羟考酮（0.1毫克/千克），并在预设时间间隔采集动脉血样。在镇痛效能研究中，患者在手术结束前30分钟静脉注射羟考酮（0.1毫克/千克），然后置于术后麻醉护理单元（PACU），并要求他们每隔10分钟使用视觉模拟量表（0 = 无疼痛，10 = 最剧烈疼痛）对疼痛进行评分。当静息时伤口疼痛和按压时伤口疼痛首次分别评为≥3或≥5时，采集第一份血样以确定MEC。在用2毫克羟考酮滴定使静息时伤口疼痛<3且伤口按压时疼痛<5后，采集第二份血样并确定MEAC。对每位患者再次测定MEC和MEAC。
在群体药代动力学研究（n = 54）中，三室乳头模型很好地描述了羟考酮血浆浓度随时间的变化。瘦体重和年龄分别是羟考酮药代动力学模型分布容积和代谢清除率的显著协变量。镇痛效能研究（n = 50）表明，中位数（95%CI）MEC和MEAC首次测量时分别为31.5（19.2 - 42.8）和74.1（29.2 - 128.3）纳克/毫升，第二次测量时分别为63.4（15.6 - 120.1）和76.1（32.9 - 132.7）纳克/毫升。
在腹部开放性大手术中，羟考酮的MEAC和镇痛效能分别为75纳克/毫升和60纳克/毫升。
