Population pharmacokinetics of intravenous acetaminophen in Japanese patients undergoing elective surgery
Population pharmacokinetics of intravenous acetaminophen in Japanese patients undergoing elective surgery
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日本择期手术患者静脉注射对乙酰氨基酚的群体药代动力学
DOI：
10.1007/s00540-017-2358-7
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发表时间：
2017
影响因子：
2.8
通讯作者：
Murakawa Masahiro
中科院分区：
文献类型：
--
作者：
Imaizumi Tsuyoshi;Obara Shinju;Mogami Midori;Iseki Yuzo;Hasegawa Makiko;Murakawa Masahiro
简介 手术期间静脉注射 (i.v.) 对乙酰氨基酚用于术后镇痛。然而，关于静脉注射的药代动力学的信息很少。对接受全身麻醉手术的日本患者使用对乙酰氨基酚。方法该研究经机构审查委员会批准并在 UMIN-CTR 注册（UMIN000013418）。计划在全身麻醉下接受择期手术的患者在获得书面知情同意后被纳入。手术期间，静脉注射 1 克。对乙酰氨基酚的给药时间超过 15、60 或 120 分钟。在开始给药后 0-480 分钟的时间点测量对乙酰氨基酚浓度（每例 15 或 16 个样品）（液相色谱-质谱/串联质谱；定量限 0.1 μg/mL）。对三个已发表的药代动力学模型的预测性能进行了评估。还使用基于 NONMEM 程序的非线性混合效应模型对群体药代动力学进行了分析。结果分析了 12 名接受内窥镜或下肢手术的患者的数据（男性/女性 = 7/5，中位年龄 55 岁，体重 63 公斤）。用瑞芬太尼和丙泊酚或七氟醚维持麻醉。静脉注射的药代动力学模型Würthwein 等报道的对乙酰氨基酚。效果很好。使用 185 个数据点，静脉注射的药代动力学。对乙酰氨基酚通过两室模型进行描述，其中体重作为协变量，但不包括年龄、性别或肌酐清除率。最终模型的中位预测误差和中位绝对预测误差分别为-1和10%。结论静脉注射的群体药代动力学模型。在日本患者中构建了对乙酰氨基酚，其性能在可接受的范围内。
IntroductionIntravenous (i.v.) acetaminophen is administered during surgery for postoperative analgesia. However, little information is available on the pharmacokinetics of i.v. acetaminophen in Japanese patients undergoing surgery under general anesthesia.MethodsThe study was approved by the Institutional Review Board and registered at UMIN-CTR (UMIN000013418). Patients scheduled to undergo elective surgery under general anesthesia were enrolled after obtaining written informed consent. During surgery, 1 g of i.v. acetaminophen was administered over 15, 60, or 120 min. Acetaminophen concentrations (15 or 16 samples per case) were measured at time points from 0−480 min after the start of administration (liquid chromatography−mass spectrometry/tandem mass spectrometry; limit of quantitation 0.1 μg/mL). The predictive performance of three published pharmacokinetic models was evaluated. Population pharmacokinetics were also analyzed using a nonlinear mixed-effect model based on the NONMEM program.ResultsData from 12 patients who underwent endoscopic or lower limb procedures were analyzed (male/female = 7/5, median age 55 years, weight 63 kg). Anesthesia was maintained with remifentanil and propofol or sevoflurane. The pharmacokinetic model of i.v. acetaminophen reported by Würthwein et al. worked well. Using 185 datapoints, the pharmacokinetics of i.v. acetaminophen were described by a two-compartment model with weight as a covariate but not age, sex, or creatinine clearance. The median prediction error and median absolute prediction error of the final model were −1 and 10%, respectively.ConclusionA population pharmacokinetic model of i.v. acetaminophen in Japanese patients was constructed, with performance within acceptable ranges.