Elkomy Mohammed H, Drover David R, Galinkin Jeffery L, Hammer Gregory B, Glotzbach Kristi L
Department of Pharmaceutics and Industrial Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305-5117, USA.
Clin Pharmacokinet. 2016 Oct;55(10):1217-1226. doi: 10.1007/s40262-016-0398-z.
The aim of this study was to characterize the relationship between morphine plasma concentration and repeated time to postoperative remedication events in children undergoing cardiac surgery.
Data from our previously published study of morphine pharmacokinetics were utilized in this pharmacodynamic study. A population survival analysis based on hazard functions was undertaken in NONMEM(®).
Hazard was best described by a Gompertz function changing in steps over time. Concentration and age were the only predictors of the hazard function. Concentration producing 50 % reduction in hazard was 19.6 (bootstrap 95 % confidence interval 5.90-49.5 ng/ml). The hazard ratio for a 1-year-old child to a 1-month-old child was 1.91 (1.35-2.86). Sensitivity to morphine decreased with age and leveled off after 1-year of life. Morphine sulfate doses >0.1 mg/kg did not noticeably increase tolerable pain durations.
Time to remedication is a clinically useful endpoint for assessing opioid-induced analgesia. Sensitivity to morphine treatment is age-dependent. Morphine sulfate doses of 0.1-0.2 mg/kg are adequate for the management of postoperative pain in children. Our findings may help avoid unnecessary large morphine doses in children.
本研究旨在描述心脏手术患儿吗啡血浆浓度与术后重复用药事件发生时间之间的关系。
本药效学研究使用了我们之前发表的吗啡药代动力学研究数据。在NONMEM®中进行基于风险函数的群体生存分析。
风险最好用随时间逐步变化的冈珀茨函数来描述。浓度和年龄是风险函数的唯一预测因素。使风险降低50%的浓度为19.6（自抽样95%置信区间5.90 - 49.5纳克/毫升）。1岁儿童与1个月大儿童的风险比为1.91（1.35 - 2.86）。对吗啡的敏感性随年龄降低，1岁后趋于平稳。硫酸吗啡剂量>0.1毫克/千克并未显著延长可耐受疼痛持续时间。
再次用药时间是评估阿片类药物诱导镇痛的一个临床有用终点。对吗啡治疗的敏感性与年龄有关。0.1 - 0.2毫克/千克的硫酸吗啡剂量足以管理儿童术后疼痛。我们的研究结果可能有助于避免儿童不必要的大剂量吗啡使用。
