Timmer C J, Srivastava N, Dieben T O, Cohen A F
N.V. Organon, Oss, The Netherlands.
Eur J Drug Metab Pharmacokinet. 1999 Oct-Dec;24(4):335-43. doi: 10.1007/BF03190042.
In a three-period cross-over study with 24 healthy young females (study part 1), the bioavailability of etonogestrel (3-ketodesogestrel) was determined after a single oral dose of two Cerazette tablets (each containing 75 microg desogestrel), one Liseta tablet (containing 150 microg desogestrel and 1.5 mg 17beta-estradiol), and an intravenous dose of 150 microg etonogestrel. Etonogestrel serum levels from 23 subjects could be analysed by radio-immunoassay. The geometric mean bioavailability of etonogestrel from Cerazette and Liseta tablets was 0.79 and 0.82, with 95% confidence intervals of 0.73-0.86 and 0.76-0.88, respectively. Also, the oral formulations were found to be bioequivalent. Subsequently, the single-dose pharmacokinetic parameters of etonogestrel from Cerazette tablets were compared with those after multiple dosing of one Cerazette tablet once daily for 7 days, in a subgroup of 12 subjects (study part 2). A steady state was observed from the fourth day of daily dosing onwards, with time-invariant parameters except for a 14% lower dose-normalised AUC. The least-squares geometric means of the elimination half-life of etonogestrel were approximately 30 h for the three single-dose treatments in study part 1, as well as for the single- and multiple-dose treatments of Cerazette in study part 2, without differences between groups.
在一项针对24名健康年轻女性的三阶段交叉研究中（研究部分1），在单次口服两片Cerazette片（每片含75微克去氧孕烯）、一片Liseta片（含150微克去氧孕烯和1.5毫克17β-雌二醇）以及静脉注射150微克依托孕烯后，测定了依托孕烯（3-酮去氧孕烯）的生物利用度。23名受试者的依托孕烯血清水平可通过放射免疫测定法进行分析。Cerazette片和Liseta片中依托孕烯的几何平均生物利用度分别为0.79和0.82，95%置信区间分别为0.73 - 0.86和0.76 - 0.88。此外，发现口服制剂具有生物等效性。随后，在12名受试者的亚组中（研究部分2），将Cerazette片中依托孕烯的单剂量药代动力学参数与每日一次服用一片Cerazette片，连续服用7天的多剂量后的参数进行了比较。从每日给药的第四天起观察到稳态，除剂量标准化AUC降低14%外，参数不随时间变化。在研究部分1的三种单剂量治疗以及研究部分2中Cerazette片的单剂量和多剂量治疗中，依托孕烯消除半衰期的最小二乘几何平均值约为30小时，各组之间无差异。
