纳布啡注射液在健康受试者中的药代动力学研究  

Pharmacokinetics of Intravenous Nalbuphine in Healthy Volunteers

作　　者：蔡立婧[1,2] 张俊[1] 彭文兴[1] 朱荣华[1] 王秀梅[1] 阳剑[1] 张啟智[1] 

机构地区：[1]中南大学湘雅二医院临床药学教研室,长沙410011 [2]江西省人民医院,南昌330006

出　　处：《中国药学杂志》2011年第20期1597-1600,共4页Chinese Pharmaceutical Journal

摘　　要：目的研究单次注射盐酸纳布啡后的药代动力学,为该药临床研究及合理用药提供依据。方法 16名健康受试者,男女各半,分为两组,采用随机、开放试验设计,试验分别单剂量注射10、20 mg的盐酸纳布啡注射液。分别于给药前及给药后0、5、10、15、30、45 min、1、1.5、2、4、6、8、12 h分别采集静脉血4 mL。采用LC-MS/MS法测定血浆样品中纳布啡的血药浓度,并计算主要的药动学参数。结果单剂量注射10、20 mg的盐酸纳布啡注射液后AUC0-12分别为(213.4±195.7)和(325.7±26.8)ng.h.mL-1,AUC0-∞分别为(218.1±200.7)和(332.0±25.8)ng.h.mL-1;t1/2分别为(2.2±0.4)和(2.2±0.2)h;V分别为(202.9±114.2)和(194.1±24.3)L;CL分别为(63.7±25.4)和(60.6±4.5)L.h-1;MRT0～12分别为(3.4±0.6)和(3.1±0.6)h。结论两种剂量的清除率、体内滞留时间和药物消除半衰期相近;与给药剂量无关,结果符合线性药动学特征。经体重与剂量校正后各剂量组受试者的药动学参数AUC0-12和AUC0-∞在性别之间无统计学差异。OBJECTIVE To assess the pharmacokinetic properties of nalbuphine after single intravenous administration in healthy Chinese volunteers.METHODS Sixteen healthy volunteers（8 males and 8 females） were enroued in this study.The 16 healthy volunteers were divided into two groups（each group consisted of 4 males and 4 females） and received intravenous administration of nalbuphine at doses of 10,20 mg,respectively.Blood samples（4 mL） were immediately collected into heparinized tubes before injection and at 0,5,10,15,30,45 min,1,1.5,2,4,6,8,12 h after injection.The pharmacokinetic parameters including ρmax,tl/2,AUC0-t,AUC0-∞,CL,V and MRT0-t were calculated.Tolerability was assessed throughout the study.RESULTS The main pharmacokinetic parameters for nalbuphine after intravenous administration at doses of 10 and 20 mg were as follows：AUC0-12（213.4±195.7） ng·h·mL-1,（325.7±26.8） ng·h·mL-1,AUC0-∞（218.1±200.7） ng·h·mL-1,（332.0±25.8） ng·h·mL-1,t1/2（2.2±0.4） h,（2.2±0.2） h,V（202.9±114.2） L,（194.1±24.3） L;CL（63.7±25.4） L·h-1 and（60.6±4.5） L·h-1,MRT0~12（3.4±0.6） h and（3.1±0.6） h.AUC0-12 and AUC0-∞ increased proportionally with the dose levels.CONCLUSION The t1/2,MRT,V and CL were very similar between 10 and 20 mg.No significant differences were observed in t1/2 values between different doses.No significant differences were found in AUC and ρmax men women after dose and body weightnormaliz.

关 键 词：纳布啡 药代动力学 液相色谱-串联质谱法 

分 类 号：R969.1[医药卫生—药理学]