盐酸氨溴索口腔崩解片在健康人体的药物动力学

Pharmacokinetics of ambroxol hydrochloride orally disintegrating tablets in healthy volunteers

目的:建立快速、灵敏的氨溴索人体内血药浓度的高效液相色谱-串联质谱测定法,观察盐酸氨溴索口腔崩解片在健康人体内的药物动力学过程。方法:于2006-03选择男性健康志愿者18名,试验前实验方案经医院伦理委员会审批,志愿者签署知情同意书后,单剂量口服盐酸氨溴索口腔崩解片3片(含盐酸氨溴索90mg)后,分别于给药前和给药后15,30,45min,1,1.5,2,2.5,3,4,6,8,10,12,14,24h采集血样。实验评估:①用高效液相色谱-串联质谱测定法测定血浆中氨溴索的浓度,绘制药-时曲线。②采用PKS程序对试验数据进行统计学分析处理,计算有关药物动力学参数。③观察药物崩解时限和不良反应情况。结果:①药-时曲线:单剂量口服盐酸氨臭索口腔崩解片(含盐酸氨溴索90mg)后,其药-时曲线拟合符合二室模型。②药物动力学参数:达峰浓度,达峰时间,清除半衰期,0～24h、0～∞h血浆药-时曲线下面积分别为(171.87±53.92)μg/L,(1.3±0.3)h,(6.9±2.7)h,(730.6±243.8)μg/(L·h),(819.4±271.6)μg/(L·h)。③药物崩解时限和不良反应:18名健康志愿者中口含受试制剂后主诉口感良好,无沙砾感,崩解时限为10～40s,平均(21±11)s。在试验的过程中,未见不良反应,试验结束后复查心肝肾功能均正常。结论:试验建立的氨溴索人体内血药浓度测定方法灵敏、快速、可靠;盐酸氨溴索口腔崩解片单剂量给药后在健康人体内药物动力学与文献报道基本一致。

AIM： To develop a rapid and sensitive high performance liquid chromatography-mass （HPLC-MS/MS） method and observe pharmacokinetics characteristics of ambroxol tablets in healthy volunteers. spectrometry hydrochloride orally disintegrating METHODS： Totally 18 male healthy volunteers were enrolled in March 2006. Experimental scheme was approved by the Ethics Committee of Guangzhou Liwan Maternal ＆ Child Hospital before trial. The volunteers signed the informed consent, and then received a single oral dose of 3 orally disintegrating tablets containing 90 mg ambroxol hydrochloride. Blood samples were collected before administration and at minutes 15, 30 and 45 and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14 and 24 hours after administration, respectively. Experimental evaluation： ①Concentration of ambroxol in plasma was measured by HPLC-MS/MS method. Concentration-time curve was drawn. ② Experimental data were statistically analyzed and pharmacokinetics parameters were calculated by PKS program. ③Disintegration time and adverse reaction were observed. RESULTS： ① Concentration-time curve： Concentration-time curve was fitted with a two-compartment model after receiving a single oral dose of 3 orally disintegrating tablets containing 90 mg ambroxol hydrochloride. ② Pharmacokinetics parameters： Maximum concentration （Cmax）, maximum time （Tmax）, Elimination half-time （T1/2）, 0-24 h area under the concentration-time curve （AUC0-24） and 0-∞ h area under the concentration-time curve （AUC0-∞） were （171.87±53.92）μg/L, （1.3±0.3） hours , （6.9±2.7） hours , （730.6±243.8） μg/ （L .h）, （819.4±271.6）μg/（L.h）, respectively.③Disintegration time and adverse reaction： The 18 healthy volunteers showed good chief complaint mouthfeel, no gravel leering, with the disintegration time of 10-40 s, mean （21 ±11 ） s. No adverse reaction was found during the trial. Heart, liver and renal function was normal after the trial. CONCLUSION： The analytical method appears to be sensitive, quick and accurate. The pharmacokinetic characteristics of a single dose of ambroxol hydrochloride orally disintegrating tablets in healthy persons are similar to that reported in literatures.