Merck & Co., Inc., Rahway, NJ, USA.
Am J Ther. 2009 Nov-Dec;16(6):487-95. doi: 10.1097/MJT.0b013e3181985130.
Laropiprant is a prostaglandin D2 receptor 1 antagonist that is being developed in combination with niacin for the treatment of dyslipidemia. This randomized clinical study evaluated the effect of laropiprant on the pharmacokinetics of ethinyl estradiol (EE) and norelgestromin (NGMN), the principal circulating metabolite of norgestimate, in healthy women receiving 3 or more months of an oral contraceptive (Ortho Tri-Cyclen; Ortho-McNeil Pharmaceutical, Raritan, NJ), which contains EE and norgestimate. Twenty-one female subjects with normal menstrual cycles received the oral contraceptive on Days 1 to 21 during two consecutive contraceptive cycles. Subjects received double-blind 40 mg/day laropiprant or placebo on Days 1 to 21 of each contraceptive cycle. Plasma samples were collected predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose on Day 21 to measure area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24hr) and maximum concentration observed in plasma (Cmax) of EE and NGMN. Comparability would be declared if the 90% confidence intervals for the geometric mean ratio of AUC0-24hr and Cmax in the absence and presence of laropiprant were within predefined bounds (0.80-1.25). The estimated geometric mean ratios (90% confidence intervals) of EE and NGMN, respectively, were 1.08 (1.04-1.13) and 0.97 (0.94-0.99) for AUC0-24hr and 1.16 (1.06-1.27) and 1.00 (0.94-1.06) for Cmax. The 90% confidence intervals for the geometric mean ratio of EE Cmax minimally exceeded the prespecified bounds; the other relevant pharmacokinetic parameters fell within the predefined bounds. Coadministration of 40 mg laropiprant with the oral contraceptive did not lead to clinically meaningful alterations in the pharmacokinetics of EE or NGMN.
拉罗匹仑是一种前列腺素 D2 受体 1 拮抗剂，与烟酸联合用于治疗血脂异常。这项随机临床试验评估了拉罗匹仑对健康女性（正在服用含有乙炔雌二醇和诺孕酯的口服避孕药，连续 3 个月或更长时间，Ortho Tri-Cyclen；Ortho-McNeil 制药公司，新泽西州 Raritan）中乙炔雌二醇（EE）和诺孕酯（NGMN）药代动力学的影响，诺孕酯是诺孕酯的主要循环代谢物。21 名具有正常月经周期的女性在两个连续的避孕周期中，于第 1 至 21 天接受口服避孕药。每个避孕周期的第 1 至 21 天，受试者接受 40mg/天的拉罗匹仑或安慰剂的双盲治疗。第 21 天，在每个避孕周期的第 21 天，在给药前、给药后 0.5、1、1.5、2、3、4、6、8、12 和 24 小时采集血浆样本，以测量从 0 到 24 小时（AUC0-24hr）的血浆浓度-时间曲线下面积和最大血浆浓度（Cmax）。如果无拉罗匹仑和有拉罗匹仑时 EE 和 NGMN 的 AUC0-24hr 和 Cmax 的几何均数比值的 90%置信区间在预定范围内（0.80-1.25），则宣布可比较。EE 和 NGMN 的估计几何均数比值（90%置信区间）分别为 AUC0-24hr 的 1.08（1.04-1.13）和 0.97（0.94-0.99）和 Cmax 的 1.16（1.06-1.27）和 1.00（0.94-1.06）。EE Cmax 的几何均数比值的 90%置信区间最小限度地超过了预定的界限；其他相关药代动力学参数在预定范围内。与口服避孕药联合使用 40mg 拉罗匹仑不会导致 EE 或 NGMN 的药代动力学发生有临床意义的改变。
