Laboratoire de Biologie Humaine, CHU Amiens-Picardie, Biologie Endocrinienne et Osseuse 1, 80 054 Amiens, France.
EA 7517, Centre de Recherche Universitaire en Santé de l'UPJV, site Hôpital Sud, 80 054 Amiens, France.
Nutrients. 2019 Mar 26;11(3):703. doi: 10.3390/nu11030703.
Vitamin D deficiency is frequent in the general population and both subjects and health professionals could benefit from a broader range of vitamin D3 formulations. We conducted a single-dose, open-label, parallel-group, randomized bioequivalence study to compare a single dose of a newly developed vitamin D3 100,000 IU in a soft capsule (Group 1) with the reference drug vitamin D3 100,000 IU oral solution in ampoule (Group 2) in healthy volunteers over a four-month period. The primary endpoint was the area under the curve (AUC) of serum 25-hydroxyvitamin-D (25(OH)D) concentrations on Day 112. This study was conducted in France from February to June 2014 in 53 young adults with a mean age of 26.9 years. At baseline, low mean serum 25(OH)D levels were observed in both groups (10.6 ng/mL in Group 1 and 9.0 ng/mL in Group 2). On Day 112, the AUC of serum 25(OH)D concentration was 2499.4 ± 463.8 nmol/mL (7.8 ± 0.2 for LogAUC) for Group 1 and 2152.3 ± 479.8 nmol/mL (7.6 ± 0.2 for LogAUC) for Group 2. Bioequivalence of the two treatments was not demonstrated. Superiority of vitamin D3 100,000 IU soft capsule was observed with = 0.029 for AUC and = 0.03 for LogAUC using a non-parametric Wilcoxon test. The profile of the serum 25(OH)D concentration showed a significant difference in favor of Group 1 on Days 1, 3, 7, 14 and 90. Mean serum 25(OH)D concentrations in Group 1 were between 20 and 30 ng/mL during the four-month period and under 20 ng/mL throughout the study in Group 2, except on Day 112. Mean C for Group 1 was significantly higher ( = 0.002). Fourteen days were needed to reach T by more than half the subjects in Group 1 compared to 45 days in Group 2. Both treatments were well tolerated, with no severe or related adverse events reported. In conclusion, the pharmacokinetic profile of the new formulation of vitamin D3 100,000 IU soft capsule is superior to that of the oral solution in ampoule. The new formulation increased serum 25(OH)D levels to above 20 ng/mL and maintained levels from 20 ng/mL to 30 ng/mL for four months in late winter and spring.
维生素 D 缺乏在普通人群中很常见，患者和医务人员都可以从更广泛的维生素 D3 制剂中受益。我们进行了一项单次、开放标签、平行组、随机生物等效性研究，比较了新开发的维生素 D3 100,000IU 软胶囊（第 1 组）与参考药物维生素 D3 100,000IU 安瓿口服液（第 2 组）在健康志愿者中的单次剂量，为期四个月。主要终点是第 112 天血清 25-羟维生素 D（25(OH)D）浓度的曲线下面积（AUC）。这项研究于 2014 年 2 月至 6 月在法国进行，共有 53 名平均年龄 26.9 岁的年轻人参加。在基线时，两组的血清 25(OH)D 水平均较低（第 1 组为 10.6ng/mL，第 2 组为 9.0ng/mL）。第 112 天，第 1 组血清 25(OH)D 浓度 AUC 为 2499.4±463.8nmol/mL（LogAUC 为 7.8±0.2），第 2 组为 2152.3±479.8nmol/mL（LogAUC 为 7.6±0.2）。两种治疗方法的生物等效性未得到证实。使用非参数 Wilcoxon 检验，第 1 组 AUC 的优势比为 =0.029，LogAUC 的优势比为 =0.03，表明维生素 D3 100,000IU 软胶囊具有优越性。第 1 组的血清 25(OH)D 浓度谱在第 1、3、7、14 和 90 天显示出显著差异。第 1 组在整个四个月期间的平均血清 25(OH)D 浓度在 20 至 30ng/mL 之间，而第 2 组在整个研究期间除第 112 天外均低于 20ng/mL。第 1 组的平均 C 显著更高（=0.002）。与第 2 组的 45 天相比，第 1 组中有超过一半的受试者需要 14 天才能达到 T。两种治疗方法均耐受良好，均未报告严重或相关的不良事件。结论：新开发的维生素 D3 100,000IU 软胶囊的药代动力学特征优于安瓿口服液。新配方将血清 25(OH)D 水平提高至 20ng/mL 以上，并在冬末和春季维持 20ng/mL 至 30ng/mL 的水平达四个月。
