沙丁胺醇定量气雾剂在健康志愿者中的药代动力学及相对生物利用度

Pharmacokinetics and relative bioavailability of salbutamol metered-dose inhaler in healthy volunteers.

作者信息

Du Xiao-Li, Zhu Zhu, Fu Qiang, Li Da-Kui, Xu Wen-Bing

机构信息

Department of Pharmacy, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.

出版信息

Acta Pharmacol Sin. 2002 Jul;23(7):663-6.

PMID:12100764

Abstract

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 two-compartment model. The parameters for salbutamol inhaled and orally administered were as following: T(max) (0.22+/-0.07) and (1.8+/-0.6) h, C(max) (3.4+/-1.1) and (3.9+/-1.4) microg/L, T(1/2) (4.5+/-1.5) and (4.6+/-1.1) h, AUC0-20 min (0.9+/-0.3) and (0.16+/-0.10) microg x h x L(-1), respectively. There were significant differences in T(max) and AUC0-20 min between the two dosage forms. The AUC0-20 min (inhal) was 8 times as high as the AUC0-20 min (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.

摘要

目的

研究沙丁胺醇定量吸入气雾剂（MDI）在健康志愿者体内的药代动力学及相对生物利用度。

方法

改进了测定人血浆中沙丁胺醇的高效液相色谱法。10名健康中国男性志愿者参加随机交叉研究。受试者吸入或口服1.2mg沙丁胺醇后，在预定时间点采集14份血样。采用非房室模型评估血浆中沙丁胺醇浓度以获得药代动力学参数。计算MDI相对于水溶液的相对生物利用度。

结果

高效液相色谱法灵敏、特异、准确、精密。沙丁胺醇MDI的药代动力学用二房室模型能很好地描述。吸入和口服沙丁胺醇的参数如下：达峰时间（T(max)）分别为(0.22±0.07)和(1.8±0.6)小时，峰浓度（C(max)）分别为(3.4±1.1)和(3.9±1.4)μg/L，半衰期（T(1/2)）分别为(4.5±1.5)和(4.6±1.1)小时，0至20分钟的药时曲线下面积（AUC0-20 min）分别为(0.9±0.3)和(0.16±0.10)μg·h·L⁻¹。两种剂型在T(max)和AUC0-20 min上有显著差异。吸入的AUC0-20 min是口服的8倍。与口服溶液相比，沙丁胺醇MDI的相对生物利用度为57%±24%。