Müller F O, Hundt H K, Luus H G, van Dyk M, Groenewoud G, van der Meer M J, Steinijans V W
S Afr Med J. 1987 Aug 1;72(3):175-8.
In a randomised, multiple-dose, cross-over study in 14 healthy volunteers, plasma theophylline concentrations were compared during a 12-hour dosing interval after repeated administration of theophylline (Euphyllin Retard; Byk Gulden) as whole and halved tablets. Bio-availability of theophylline from the halved tablets relative to the whole tablets was: 116% (100%, 134%) for the extent of absorption as judged by the area under the concentration time curve (AUC) and 115% (99%, 135%) for the rate of absorption as judged by maximum concentration (Cmax). The confidence levels for the 80-120% bio-equivalence range were 72% (AUC) and 76% (Cmax), those for the 80 and 125% range were 91% (AUC) and 91% (Cmax). The plateau times T75% Cmax, which characterise the sustained-released properties, were 8.5 +/- 2.9 hours (halved) and 8.3 +/- 2.5 hours (whole) during the 12-hour dosing interval. It is concluded that no clinically relevant deviations in steady-state plasma theophylline concentration and sustained-release properties are likely to result from breaking (halving) the film-coated tablets.
在一项针对14名健康志愿者的随机、多剂量、交叉研究中，比较了在重复服用氨茶碱（长效优喘平；拜耳先灵）整片和半片后的12小时给药间隔期间的血浆氨茶碱浓度。相对于整片，半片氨茶碱的生物利用度为：以浓度-时间曲线下面积（AUC）判断的吸收程度为116%（100%，134%），以最大浓度（Cmax）判断的吸收速率为115%（99%，135%）。80 - 120%生物等效性范围的置信水平，AUC为72%，Cmax为76%；80%至125%范围的置信水平，AUC为91%，Cmax为91%。在12小时给药间隔期间，表征缓释特性的达峰时间T75% Cmax，半片为8.5±2.9小时，整片为8.3±2.5小时。得出的结论是，掰开（切成半片）薄膜包衣片不太可能导致稳态血浆氨茶碱浓度和缓释特性出现临床相关偏差。
