硫酸沙丁胺醇缓释片的制备及其在健康人体内的药动学研究

Study on Sustained Release Tablets of Salbutamol Sulfate and Its Pharmacokinetics in Healthy Human Volunteers

制备了硫酸沙丁胺醇骨架型缓释片（８ｍｇ／片），以释放度为指标筛选出了适宜处方，并对该处方缓释片与市售普通片对照进行了健康人体单剂量及多剂量随机交叉给药药动学研究。用高效液相荧光色谱法测定了血浆中的药物浓度。缓释片的药动学参数Ｔｍａｘ，Ｃｍａｘ，ＡＵＣ０→∞及ＰＴＦ（波动分数）分别为（４．６±０．８）ｈ，（７．９±１．４）ｎｇ／ｍｌ，（１２１．１±１２．３）ｈ·ｎｇ／ｍｌ及０．９３±０．２６，而普通片的相应药动学参数则分别为（１．４±０．４）ｈ，（１５．１±２．４）ｎｇ／ｍｌ，（１０３．３±８．７）ｈ·ｎｇ／ｍｌ及１．３１±０．２７。经双单侧检验两制剂ＡＵＣ０→∞无显著性差异，而ＰＴＦ则有显著性差异。缓释片相对于普通片的生物利用度为１０６．０％。缓释片具有给药次数少（一日二次）、给药后血药浓度波动较小的特点。

Hydrophilic gel matrix tablets of salbutamol sulfate(SRT) were developed. Formulation of SRT was selected by determination of the release rate. It was found that the ratio of hydrophilic HPMC to hydrophobic stearic alcohol could be a key to the establishment of SRT matrix. The bioavailability of SRT was compared with conventional tablets(CT) in 10 healthy human volunteers under randomized crossover design. Each subject orally received 8 mg of SRT and 7.2 mg of CT for single dose administration, and received 8 mg of SRT every 12 h and 4.8 mg of CT every 8 h for multiple dose administration. Plasma concentrations were determined by HPLC with fluorescence detection. The parameters of SRT, T max and C max , were found to be (4.60±0.8)h and (7.9±1.4) ng/ml respectively. The relative bioavailability of SRT was 106.0%, compared to CT. No statistically significant difference was observed in AUC 0→∞ , but difference was found in peak to trough fluctuation( PFT ). It was concluded that twice daily administration of SRT provided a better altenative than three or four times daily administration of CT.