Jeon Ji-Young, Lee Sun Young, Im Yong-Jin, Kim Eun-Young, Kim Yunjeong, Park Tae Sun, Chae Soo-Wan, Lee Jae Won, Jun Hun, Lee Tae Won, Kim Min-Gul
Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.
Clinical Trial Center and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea; Department of Radiation Oncology, Chonbuk National University, Jeonju, Republic of Korea.
Clin Ther. 2014 Jan 1;36(1):48-57. doi: 10.1016/j.clinthera.2013.12.001. Epub 2013 Dec 28.
Combined treatment with a bisphosphonate and vitamin D has been proposed for postmenopausal osteoporosis. A new, fixed-dose combination tablet of ibandronate plus vitamin D3 has been developed for monthly administration to treat postmenopausal osteoporosis.
The main objective of the present study was to compare the pharmacokinetics of vitamin D3 administered in 2 forms: a newly developed ibandronate 150-mg/vitamin D3 24,000-IU tablet (DP-R206, test drug) and a stand-alone vitamin D3 24,000-IU tablet (reference drug). A secondary objective was to evaluate the safety and tolerability of DP-R206 in healthy adult male Korean volunteers.
This study was a single-dose, open-label, randomized-sequence, 2-treatment, 2-way crossover trial. Blood samples were collected from 24 hours' predose to 120 hours' postdose. The plasma concentrations of vitamin D3 were analyzed by using a validated HPLC-MS/MS method. Pharmacokinetic parameters were calculated, and the 90% CIs of the ratios of the geometric means of the parameters were determined from the logarithmically transformed data by using ANOVA.
Thirty-sex healthy adult male Korean volunteers with a mean (SD) age of 25.8 (2.7) years, a mean height of 174.0 (5.9) cm, and a mean weight of 69.1 (6.2) kg were enrolled; 29 participants completed the study. The 90% CIs of the ratios of the geometric means (test drug/reference drug) of the baseline-corrected Cmax, AUC0-last, and AUC0-∞ values were 0.93 to 1.24, 0.89 to 1.19, and 0.87 to 1.18, respectively. The 90% CIs of the ratios of the geometric means (test drug/reference drug) of the baseline-uncorrected Cmax, AUC0-last, and AUC0-∞ values were 0.93 to 1.24, 0.88 to 1.19, and 0.87 to 1.18, respectively. Eighty-four adverse events (AEs) were reported in 24 of 32 subjects receiving DP-R206, and 14 AEs were reported in 8 of 29 subjects receiving the vitamin D3 24,000-IU tablet. All of the subjects who experienced AEs recovered without sequelae, and no serious AEs were observed.
The vitamin D3 pharmacokinetics were similar for DP-R206 and the 24,000-IU vitamin D3 tablet. DP-R206 was well tolerated.
已有人提出双膦酸盐与维生素D联合治疗绝经后骨质疏松症。已研发出一种新的固定剂量组合片剂，即伊班膦酸钠加维生素D3，用于每月给药以治疗绝经后骨质疏松症。
本研究的主要目的是比较以两种形式给药的维生素D3的药代动力学：一种新研发的伊班膦酸钠150毫克/维生素D3 24000国际单位片剂（DP-R206，试验药物）和一种单独的维生素D3 24000国际单位片剂（参比药物）。次要目的是评估DP-R206在健康成年韩国男性志愿者中的安全性和耐受性。
本研究为单剂量、开放标签、随机序列、双治疗、双向交叉试验。在给药前24小时至给药后120小时采集血样。采用经过验证的高效液相色谱-串联质谱法分析血浆中维生素D3的浓度。计算药代动力学参数，并通过方差分析从对数转换数据中确定参数几何均值比值的90%置信区间。
纳入了36名健康成年韩国男性志愿者，平均（标准差）年龄为25.8（2.7）岁，平均身高为174.0（5.9）厘米，平均体重为69.1（6.2）千克；29名参与者完成了研究。基线校正后的Cmax、AUC0-last和AUC0-∞值的几何均值比值（试验药物/参比药物）的90%置信区间分别为0.93至1.24、0.89至1.19和0.87至1.18。未校正基线的Cmax、AUC0-last和AUC0-∞值的几何均值比值（试验药物/参比药物）的90%置信区间分别为0.93至1.24、0.88至1.19和0.87至1.18。在接受DP-R206的32名受试者中的24名中报告了84例不良事件（AE），在接受维生素D3 24000国际单位片剂的29名受试者中的8名中报告了14例AE。所有发生AE 的受试者均康复且无后遗症，未观察到严重AE。
DP-R206与2
4000国际单位维生素D3片剂的维生素D3药代动力学相似。DP-R206耐受性良好。
