Bayer HealthCare Pharmaceuticals, Berlin, Germany.
Clin Drug Investig. 2012 Oct 1;32(10):673-84. doi: 10.1007/BF03261921.
Neural tube defects (NTDs) are congenital malformations that occur during early embryonic development. Suboptimal maternal folate status is a well-known risk factor for the occurrence of NTDs, and periconceptional folic acid supplementation has been shown to reduce the risk of NTDs. Folate-supplemented oral contraceptives (OCs) offer a means of improving folate status in women of childbearing potential by increasing their likelihood of having raised folate levels at the time of conception.
This study aimed to demonstrate bioequivalence of ethinylestradiol (EE), drospirenone and L-5-methyl-tetrahydrofolate (L-5-methyl-THF; active moiety of levomefolate calcium) when taken as a new folate-supplemented OC containing EE/drospirenone/levomefolate calcium, with the respective OC containing EE/drospirenone and a tablet containing levomefolate calcium only.
This was a randomized, open-label, three-period crossover study carried out at a single centre in Germany. The study included 45 healthy women (age range 18-38 years). The women were randomly assigned to single doses of (i) EE 0.03 mg/drospirenone 3 mg/levomefolate calcium 0.451 mg (SAFYRAL®), (ii) EE 0.03 mg/drospirenone 3 mg (Yasmin®), and (iii) levomefolate calcium 0.451 mg, administered using a crossover design, with one or more menstrual cycle washout between doses. The primary variables were maximum concentrations (C(max)) and area under the concentration versus time curve (AUC) values for EE, drospirenone and L-5-methyl-THF.
The bioavailability of EE and drospirenone was similar after administration of EE/drospirenone/levomefolate calcium and EE/drospirenone. The geometric mean ratios (GMRs) and its 90% confidence intervals (CIs) for AUC values and C(max) were within the pre-specified range (80.00-125.00%) for bioequivalence for EE and drospirenone in both formulations. The bioavailability of L-5-methyl-THF was similar after administration of EE/drospirenone/levomefolate calcium and levomefolate calcium. The respective GMRs and 90% CIs of baseline-uncorrected and -corrected AUC(last) (AUC from time zero to time of last measurable concentration) and C(max) were also within the 80.00-125.00% range.
The novel folate-supplemented OC EE/drospirenone/levomefolate calcium is bioequivalent to the established OC Yasmin® (EE/drospirenone components) and to levomefolate calcium (folate component).
神经管缺陷（NTDs）是一种发生在胚胎早期发育过程中的先天性畸形。母体叶酸状态不佳是 NTDs 发生的一个众所周知的风险因素，而围孕期补充叶酸已被证明可以降低 NTDs 的风险。含有叶酸的口服避孕药（OCs）通过增加受孕时叶酸水平升高的可能性，为有生育能力的妇女改善叶酸状况提供了一种方法。
本研究旨在证明新型叶酸补充 OC（含 EE/drospirenone/levomefolate calcium）中 EE、屈螺酮和 L-5-甲基四氢叶酸（L-5-甲基-THF；左甲状腺素钙的活性成分）的生物等效性，与各自含有 EE/drospirenone 和仅含有左甲状腺素钙的 OC 相比。
这是一项在德国一家单一中心进行的随机、开放标签、三周期交叉研究。该研究包括 45 名健康女性（年龄 18-38 岁）。这些女性被随机分配单次剂量（i）EE 0.03mg/drospirenone 3mg/levomefolate calcium 0.451mg（SAFYRAL®）、（ii）EE 0.03mg/drospirenone 3mg（Yasmin®）和（iii）左甲状腺素钙 0.451mg，采用交叉设计给药，每个剂量之间有一个或多个月经周期洗脱期。主要变量为 EE、屈螺酮和 L-5-甲基-THF 的最大浓度（C(max)）和浓度-时间曲线下面积（AUC）值。
EE/drospirenone/levomefolate calcium 和 EE/drospirenone 给药后 EE 和屈螺酮的生物利用度相似。AUC 值和 C(max)的几何均数比值（GMR）及其 90%置信区间（CI）在 EE 和屈螺酮两种制剂的生物等效性预设范围（80.00-125.00%）内。EE/drospirenone/levomefolate calcium 给药后 L-5-甲基-THF 的生物利用度与左甲状腺素钙相似。未校正和校正基线的 AUC(last)（从时间零到最后可测量浓度的时间的 AUC）和 C(max)的相应 GMRs 和 90%CI 也在 80.00-125.00%范围内。
新型叶酸补充 OC EE/drospirenone/levomefolate calcium 与已确立的 OC Yasmin®（EE/drospirenone 成分）和左甲状腺素钙（叶酸成分）具有生物等效性。
