Clinical trial of risedronate in Japanese volunteers: single and multiple oral dose studies
Clinical trial of risedronate in Japanese volunteers: single and multiple oral dose studies
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DOI：
10.1007/s00774-003-0458-y
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发表时间：
2004-03-01
影响因子：
3.3
通讯作者：
Orimo, H
中科院分区：
文献类型：
--
作者：
Ogura, Y;Gonsho, A;Orimo, H
在健康成年男性志愿者中检查了单次口服给药后和多次口服给药期间利塞膦酸盐的耐受性和药代动力学。在单剂量研究中，剂量从 1 mg 逐渐增加至 2.5、5、10 或 20 mg。随后，利塞膦酸钠分多次给药，每次5mg，每日1次，连续7天。观察到的不良事件（其因果关系可能相关或未知）包括头痛、腹泻、体温升高、CK-BB 升高和尿 B-2-微球蛋白排泄率升高。然而，这些不良事件均无临床意义。因此，结果表明，当单次给药高达 20 mg 或多次给药高达 5 mg/天时，利塞膦酸盐具有良好的耐受性。在多剂量研究中，尿脱氧吡啶啉的变化表明利塞膦酸盐具有抗骨吸收活性。在单剂量研究中，利塞膦酸钠1、2.5、5、10和20 mg给药后，AUC和C-max呈剂量依赖性增加，而T-max、t(1/2)和尿排泄率几乎恒定。因此，利塞膦酸盐的药代动力学曲线被认为在高达 20 mg 的剂量范围内显示出线性。此外，多次给药研究的结果表明，利塞膦酸盐的血浆浓度在给药第4天达到稳定状态。日本人群服用 2.5 mg 利塞膦酸后，利塞膦酸的血浆浓度几乎与英国研究人群服用 5 mg 利塞膦酸后的血清浓度相当。
The tolerability and pharmacokinetics of risedronate after a single oral administration and during multiple oral administrations were examined in healthy adult male volunteers. In the single dose study, the dose was increased gradually from 1 mg to 2.5, 5, 10, or 20 mg. Subsequently, risedronate was given by multiple administration, 5 mg per dosing, once daily, for 7 days. The observed adverse events, whose causality was possibly related or unknown, included headache, diarrhea, increased body temperature, increased CK-BB, and increased urinary B-2-microglobulin excretion rate. However, none of these adverse events was clinically significant. The results thus showed that risedronate was well tolerated when delivered as a single administration of up to 20 mg or as a multiple administration of up to 5 mg/day. In the multiple dose study, changes in urinary deoxypyridinoline suggested the bone antiresorptive activity of risedronate. In the single dose study, AUC and C-max, after the administration of risedronate at 1, 2.5, 5, 10, and 20 mg, increased dose dependently, and the T-max, t(1/2), and urinary excretion rates were nearly constant. Therefore, the pharmacokinetic profile of risedronate was considered to show linearity in a dosage range of up to 20 mg. Furthermore, the results obtained in the multiple administration study indicated that the plasma concentrations of risedronate reached a steady state on day 4 of administration. The plasma concentrations of risedronate after the administration of 2.5 mg risedronate to the Japanese population were nearly comparable to the serum concentrations after the administration of 5 mg risedronate to the United Kingdom study population.