Lal J, Nitynand S, Asthana O P, Nagaraja N V, Gupta R C
Pharmacokinetics & Metabolism Division, Central Drug Research Institute, Lucknow, India.
Contraception. 2001 Jan;63(1):47-51. doi: 10.1016/s0010-7824(00)00189-x.
Centchroman (Ormeloxifene), a non-steroidal oral contraceptive, is used at a dose of 30 mg once a week. To prevent failures in the beginning of the therapy, it is recommended that a dose of 30 mg twice a week for 12 weeks be administered to build up adequate blood levels. The present study was undertaken to simplify the dosing schedule without sacrificing the purpose of twice a week dosing regimen, using modeling and measurement approaches. The drug was given to 60 female volunteers who were divided into seven groups: group I, 30 mg weekly; group II, 30 mg twice a week; group III, 30 mg twice a week for 12 weeks followed by 30 mg weekly; group IV, 30 mg twice a week for 6 weeks followed by 30 mg weekly; group V, 60 mg weekly; and groups VI and VII, single 60 mg loading dose followed by 30 mg weekly doses. The blood samples were collected and analyzed by HPLC. In group I, mean trough concentrations of centchroman and its active metabolite, 7-desmethyl centchroman, were comparable to the steady-state trough concentrations in groups III, IV, VI, and VII. The metabolite to parent drug ratio remained constant in all the groups. The pharmacokinetic parameters in group VII were comparable to those reported after a single 30 mg dose. Dosage regimen VI was more convenient and provided better pregnancy protection (Pearl index 1.18; unpublished report) than regimen III, which is currently on the market and, thus, could be effectively used for contraception.
醋酸棉酚（奥美昔芬）是一种非甾体类口服避孕药，每周服用一次，剂量为30毫克。为防止治疗初期出现避孕失败的情况，建议在开始的12周内每周服用30毫克，每日两次，以建立足够的血药浓度。本研究旨在通过建模和测量方法简化给药方案，同时不影响每周两次给药方案的目的。将药物给予60名女性志愿者，她们被分为七组：第一组，每周30毫克；第二组，每周两次，每次30毫克；第三组，每周两次，每次30毫克，共12周，之后每周30毫克；第四组，每周两次，每次30毫克，共6周，之后每周30毫克；第五组，每周60毫克；第六组和第七组，单次服用60毫克负荷剂量，之后每周服用30毫克。采集血样并通过高效液相色谱法进行分析。在第一组中，醋酸棉酚及其活性代谢物7-去甲基醋酸棉酚的平均谷浓度与第三组、第四组、第六组和第七组的稳态谷浓度相当。所有组中代谢物与母体药物的比例保持恒定。第七组的药代动力学参数与单次服用30毫克剂量后报告的参数相当。给药方案VI比目前市场上的方案III更方便，且提供了更好的避孕保护（Pearl指数为1.18；未发表报告），因此可有效用于避孕。
