机械通气条件下狗吗啡超声雾化吸入的药物动力学研究  

Phamacokinetics of nebulized versus intravenous morphine in dogs

作　　者：潘琳[1] 汪小海[1] 徐鑫[1] 袁盛华[1] 王丽君[1] 

机构地区：[1]南京大学医学院附属鼓楼医院麻醉科,南京210008

出　　处：《南京大学学报（自然科学版）》2008年第3期326-331,共6页Journal of Nanjing University（Natural Science）

基　　金：南京市卫生局项目(YKK05106)

摘　　要：研究机械通气条件下吗啡超声雾化吸入在狗体内的药物动力学特点,为临床应用超声雾化吸入吗啡镇痛提供参考依据.6只健康成年狗在机械通气条件下随机交叉应用超声雾化器吸入吗啡(试验组)和微量输液泵恒速泵入吗啡(对照组).分别于以下时点取右股动脉血:给药前、给药期间(10 min)每分钟和给药后2、5、7、10、15、20、45、60、90、120、150、180、240和360 min,用反相高效液相法RP-HPLC测定血浆吗啡浓度,用DAS分析软件1.0版本分析药物代谢动力学参数.结果发现,两组吗啡的曲线下面积AUC和清除率CL无显著性差异(P>0.05),试验组的半衰期T1/2为(21.9±5.1)min比对照组的(3.3±1.0)min显著延长,而且体内滞留时间MRT为(59±14)min显著长于对照组的(19±4)min(P<0.05).吗啡超声雾化吸入的绝对生物利用度为71%±20%.机械通气条件下吗啡超声雾化吸入在狗体内能迅速完全吸收,并且具有缓释效应,能够较长时间维持吗啡的有效血药浓度,可获得较高的生物利用度.In recent years, pulmonary morphine delivery has been regarded as a novel method of administration to treat severe acute or chronic pain without inducing side effects that might be encountered if given by traditional ways. But reported pulmonary delivery equipments were open systems, which may lead to nebulized morphine leakage and absorption by upper respiratory tract. We carried out this study to investigate the pharmacokinetics of single--dose nebulized versus intravenous morphine in dogs undergoing mechanical ventilation. Six healthy dogs were assigned to two groups （n=3 in each group） randomly. After tracheal intubation and mechanical ventilation the subjects received single dose 0.66 mg/kg morphine within 10 minutes during intravenous anaesthesia either by inhalation with the ultrasonic nebulizer placed between the tracheal tube and the respirator or by intravenous injection. After a one-week washout period, a crossover was made. Arterial blood samples of 1 mL were performed every minute during administration and at 2, 5, 7, 10, 15, 20, 45, 60, 90, 120, 150, 180, 240 and 360 min following administration for determination of morphine concentration by RP--HPLC. The pharmacokinetie analyses were performed by Drug and Statistics Verl. 0 using mixed-effect models. AUC, Tmax, Cmax, and MRT （0-t） were obtained by statistical moment analysis. Otherwise, T1/2 and CL were obtained according to compartment model analysis. The main pharmaeokinetic parameters of morphine after a single dose inhalation and intravenous infusion were as follows： MRT （59±14）min and （19±4）min, T1/2 （21.9±5.1）min and （3.3±1.0）min, Tmax （23.0±2.7）min and （8.8±2.4）min, Cmax （0. 245±0. 09）mg/L and （1.09±0. 32）rag/L, AUC0--∞（9.7±1.1） mg. min/L and （15.2±7. 2）mg· rain/L, CL （0. 069±0. 019）L/（min · kg） and （0. 063±0. 028）L/（min · kg） respectively and the absolute bioavailability of nebulized morphine 71%± 20%. There was a rapid appearance of morphine in plasma afte

关 键 词：吗啡 超声雾化 麻醉 狗 药物动力学 机械通气 

分 类 号：R969.1[医药卫生—药理学]