Jonkman J H, Steinijans V W, Beier W, van der Boon W J, Crasmeijer G
Pharma Bio-Research Int'l B.V., Department of Biopharmaceutics, Assen, The Netherlands.
Biopharm Drug Dispos. 1989 Mar-Apr;10(2):213-24. doi: 10.1002/bdd.2510100210.
In a multiple dose cross-over experiment in 12 healthy male adults the bioavailability and sustained release characteristics of new once daily BY912 400 mg theophylline capsules (= B, Byk Gulden Research Laboratories, FRG) were studied using Theo-24 capsules (= T, Searle & Co., USA) as reference. Both products were given once daily for a period of 7 days as an 800 mg theophylline dose at 8 am, half an hour after a standardized breakfast. Theophylline concentrations in plasma were measured on days 1, 6, and 7 using high-performance liquid chromatography. Significantly better sustained release characteristics, resulting in longer plateau time (t75%, 11.6 vs 9.2 h on day 6 and 13.1 vs 8.8 h on day 7) and smaller per cent peak-trough fluctuation in the steady state (per cent PTF, 80 vs 103 per cent on day 6 and 66 vs 100 per cent on day 7), were found for B in comparison with T. The extent of absorption on both days, however, was smaller for B compared with T (relative bioavailability 84 per cent and 81 per cent, respectively). In conclusion, the absorption of theophylline from B resulted in a more extended shape of the plateau phase, indicating better sustained release characteristics. The extent of absorption, however, over the dosing intervals was more complete with T.
在一项针对12名健康成年男性的多剂量交叉实验中，以美国先灵葆雅公司的Theo-24胶囊（=T）作为对照，研究了德国拜耳古登研究实验室生产的新型每日一次的400毫克BY912茶碱胶囊（=B）的生物利用度和缓释特性。两种产品均在标准早餐后半小时，于上午8点以800毫克茶碱剂量每日给药一次，持续7天。在第1、6和7天使用高效液相色谱法测量血浆中的茶碱浓度。与T相比，B具有显著更好的缓释特性，导致更长的平台期（第6天t75%为11.6小时对9.2小时，第7天为13.1小时对8.8小时）以及稳态下更小的峰谷波动百分比（第6天峰谷波动百分比为80%对103%，第7天为66%对100%）。然而，与T相比，B在两天内的吸收程度均较小（相对生物利用度分别为84%和81%）。总之，B中茶碱的吸收导致平台期形状更延长，表明缓释特性更好。然而，在给药间隔期间，T的吸收程度更完全。
