沙丁胺醇气雾剂在健康受试者体内的药物动力学和相对生物利用度

摘要

目的:研究沙丁胺醇气雾剂在健康受试者的药物动力学和生物利用度.方法:十名健康男性志愿者单剂量吸入1.2 mg沙丁胺醇气雾剂或口服沙丁胺醇水溶液.用HPLC法测定人血浆中沙丁胺醇浓度.以非房室模型计算药物动力学参数,计算气雾剂相对水溶液的生物利用度.结果:气雾剂和口服溶液的药物动力学参数如下:Tmax(0.22±0.07)和(1.8±0.6)h,Cmax(3.4±1.1)和(3.9±1.4)μg@L-1,T1/2(4.5±1.5)和(4.6±1.1)h,AUC0-20min(0.9±0.3)和(0.16±0.10)μg@h@L-1.两种给药途径的Tmax和AUC0-20min之间差异显著(P＜0.01).AUC0-20min(inhal)为AUC0-20min(po)的8倍.沙丁胺醇气雾剂相对口服溶液的生物利用度为57%±24%.结论:沙丁胺醇气雾剂在人体的吸收过程与口服溶液差异有显著性.%AIM: To study the pharmacokinetics and relative bioavailability of salbutamol metered-dose inhaler (MDI)in healthy volunteers. METHODS: An HPLC method for the determination of salbutamol in human plasma was improved. Ten healthy male Chinese volunteers were enrolled in a randomized crossover study. After the subjects inhaled or orally administered 1.2 mg salbutamol, fourteen blood samples were collected at predetermined time points. The concentrations of salbutamol in plasma were assessed with non-compartment model to obtain the pharmacokinetic parameters. The relative bioavailability of MDI versus water solution was calculated. RESULTS: The HPLC assay was sensitive, specific, accurate, and precise. The pharmacokinetics of salbutamol MDI was described well with twocompartment model. The parameters for salbutamol inhaled and orally administered were as following: Tmax (0.22±0.07) and (1.8±0.6) h, Cmax(3.4± 1.1) and (3.9±1.4) μg@L-1, T1/2(4.5±1.5) and (4.6±1.1)h, AUC0-20min(0.9±0.3) and (0.16±0.10) μg@h@L-1, respectively. There were significant differences in Tmax and AUC0-20 min between the two dosage forms.The AUC0-20min ( inhal ) was 8 times as high as the AUC0-20min (po). The relative bioavailability of salbutamol MDI was 57 % ± 24 % compared with oral solution. CONCLUSION: The absorption process of salbutamol MDI in human was significantly different from that of oral solution.