Lipworth B J, Clark R A, Dhillon D P, Charter M K, Palmer J B, McDevitt D G
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, UK.
Eur J Clin Pharmacol. 1989;37(1):49-52. doi: 10.1007/BF00609424.
Fifteen patients with asthma were given salbutamol controlled-release (SCR) 4 mg or 8 mg twice daily for seven days, in a randomised double-blind cross-over design. Plasma salbutamol levels were measured after the first and fifteenth doses for a 12 h period following drug ingestion. At steady-state the geometric mean values for Cmax were 8.2 ng/ml for 4 mg, and 16.1 ng/ml for 8 mg. Median tmax values were 300 and 240 min respectively. The geometric mean AUC (0-12) were 4507 ng.min.ml-1 and 8980 ng.min/ml. Peak to trough fluctuation ratios were 0.577 and 0.572. There were no significant differences between 4 mg or 8 mg formulations, for any of the parameters measured, after appropriate corrections for dose. The concentration-time profiles at steady-state showed little fluctuation in plasma salbutamol levels over the twelve hour dosing interval. These results show that 4 mg and 8 mg formulations of SCR provide smooth plasma profiles at steady-state with a twice daily dosing regime.
15名哮喘患者采用随机双盲交叉设计，每天两次服用4毫克或8毫克的沙丁胺醇控释制剂（SCR），共七天。在首次和第十五次给药后，于服药后12小时内测量血浆沙丁胺醇水平。在稳态时，4毫克剂量的Cmax几何平均值为8.2纳克/毫升，8毫克剂量的为16.1纳克/毫升。tmax中位数分别为300分钟和240分钟。几何平均AUC(0 - 12)分别为4507纳克·分钟·毫升⁻¹和8980纳克·分钟/毫升。峰谷波动比分别为0.577和0.572。在对剂量进行适当校正后，4毫克或8毫克制剂在所测量的任何参数方面均无显著差异。稳态时的浓度-时间曲线显示，在12小时给药间隔内，血浆沙丁胺醇水平波动很小。这些结果表明，4毫克和8毫克的SCR制剂在每日两次给药方案下，稳态时可提供平稳的血浆曲线。
