Hooper W D, Eadie M J, Dickinson R G
Department of Medicine, University of Queensland, Royal Brisbane Hospital, Herston, Australia.
Biopharm Drug Dispos. 1991 Nov;12(8):577-82. doi: 10.1002/bdd.2510120804.
A comparative bioavailability study was conducted with two capsule formulations of danazol (200 mg) in 16 healthy adult male volunteers. Fasting subjects received single doses (400 mg) of each formulation on separate occasions 1 week apart. Blood samples were drawn at specified times up to 32 h after the dose and danazol concentrations in plasma were determined by a specific and sensitive HPLC method. The results for one subject were excluded as outlier values. The data from the other 15 subjects showed small differences, which did not achieve statistical significance between the formulations with respect to Cmax, Tpeak and AUC0-infinity. The mean elimination half-life for danazol was 9.44 +/- SD 2.74 h and the mean apparent total body clearance was 710 +/- SD 2161 h-1. These data differed from previously published results, probably as a result of the more sensitive and specific assay method used in the present work. It is likely that a high proportion of the oral dose of danazol is eliminated by presystemic metabolism.
在16名健康成年男性志愿者中进行了达那唑（200mg）两种胶囊制剂的生物利用度比较研究。空腹受试者在相隔1周的不同时间分别接受单剂量（400mg）的每种制剂。在给药后长达32小时的特定时间采集血样，并通过一种特异且灵敏的高效液相色谱法测定血浆中的达那唑浓度。一名受试者的结果作为异常值被排除。其他15名受试者的数据显示差异较小，两种制剂在Cmax、Tpeak和AUC0至无穷大方面未达到统计学显著性。达那唑的平均消除半衰期为9.44±标准差2.74小时，平均表观全身清除率为710±标准差2161 h-1。这些数据与先前发表的结果不同，可能是由于本研究中使用了更灵敏和特异的测定方法。达那唑口服剂量的很大一部分可能通过首过代谢消除。
