Akagi Yuuki, Sakaue Tomoyuki, Yoneyama Eiji, Aoyama Takao
Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
Yakugaku Zasshi. 2011;131(5):801-7. doi: 10.1248/yakushi.131.801.
Alendronate, an oral bisphosphonate (e.g., Fosamax(®)), is effective in the treatment of osteoporosis, and the Fosamax(®) package insert advises that the bioavailability is reduced when taken with mineral water containing high levels of metal cations (Ca(2+), Mg(2+), etc.). However, standards regarding the water used when taking alendronate are unclear. In this study, the influence of mineral water on the absorption of oral alendronate was investigated based on urinary excretion of its unchanged form in rats. Alendronate was diluted in each water sample and administered orally (0.7 mg/kg) to male Wistar rats after 24-hour fast. Urine samples were collected until 24 h after dosing. Urine samples were alkalinized, and alendronate in urine was precipitated as a calcium salt, followed by loading on an anion exchange cartridge. Eluted alendronate was derivatized with 9-fluorenylmethoxycarbonyl (Fmoc) chloride and determined by HPLC with fluorescent detection. Cumulative urinary excretion recoveries of alendronate were calculated from the amounts of urinary excretion. Alendronate was rapidly excreted in the first 6 h, and similar elimination rate constants were seen (from 0.28 to 0.45 h(-1/2)) among the water samples. Cumulative urinary excretion recoveries with tap water, evian(®) and 100% deep ocean water were 0.98±0.17%, 0.80±0.18% and 1.01±0.16% (mean±S.E., n=4). Those with Contrex(®) (0.33±0.07%) were significantly lower when compared with ultrapure water (1.56±0.35%, p<0.01). These findings suggest that the absorption of alendronate decreases based on the calcium concentration of mineral water. In conclusion, mineral water containing high levels of calcium is not recommended when alendronate is taken.
阿仑膦酸钠是一种口服双膦酸盐（如福善美（Fosamax®）），对骨质疏松症的治疗有效，福善美（Fosamax®）的药品说明书提示，与含有高浓度金属阳离子（Ca(2+)、Mg(2+)等）的矿泉水一起服用时，其生物利用度会降低。然而，服用阿仑膦酸钠时所用水的标准尚不清楚。在本研究中，基于大鼠口服阿仑膦酸钠原形的尿排泄情况，研究了矿泉水对其吸收的影响。将阿仑膦酸钠稀释于各水样中，雄性Wistar大鼠禁食24小时后口服给药（0.7mg/kg）。给药后收集尿液样本直至24小时。将尿液样本碱化，尿中的阿仑膦酸钠以钙盐形式沉淀，然后加载到阴离子交换柱上。洗脱的阿仑膦酸钠用9-芴甲氧羰基（Fmoc）氯衍生化，并用荧光检测的高效液相色谱法测定。根据尿排泄量计算阿仑膦酸钠的累积尿排泄回收率。阿仑膦酸钠在最初6小时内迅速排泄，各水样间的消除速率常数相似（0.28至0.45h(-1/2)）。自来水、依云（evian®）和100%深层海水的累积尿排泄回收率分别为0.98±0.17%、0.80±0.18%和1.01±0.16%（平均值±标准误，n=4）。与超纯水（1.56±0.35%）相比，Contrex®（0.33±0.07%）的回收率显著降低（p<0.01）。这些发现表明，阿仑膦酸钠的吸收会因矿泉水的钙浓度而降低。总之，服用阿仑膦酸钠时不建议使用含钙量高的矿泉水。
