Peking Union Medical College Hospital, Clinical Pharmacological Research Center, Beijing, China.
Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, Beijing, China.
Clin Pharmacol Drug Dev. 2018 Sep;7(7):744-750. doi: 10.1002/cpdd.434. Epub 2018 Feb 14.
Odanacatib (ODN), an oral selective inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this phase 1 open-label study, 12 healthy Chinese postmenopausal women received single-dose ODN 50 mg on day 1 and multiple-dose ODN 50 mg once weekly on days 15, 22, 29, and 36 under fasted conditions. Pharmacokinetic (PK) parameters were evaluated on days 1 and 36. Multiple-dose area under the concentration-time profile (AUC ) and maximum plasma concentration (C ) were compared with historical data from 9 non-Chinese postmenopausal women who also received ODN 50 mg once weekly for 4 weeks. Median time to C (t ) was 3 and 4 hours following single- and multiple-dose administration, respectively. The arithmetic mean ± SD terminal half-life was 81.0 ± 14.0 and 106.7 ± 14.4 hours following single- and multiple-dose administration, respectively. Comparison of multiple-dose PK parameters showed that the geometric mean ratios (Chinese/non-Chinese) and 95%CIs for AUC and C were 0.81 (0.55-1.19) and 0.87 (0.69-1.11), respectively. All adverse events were mild, none were serious, and none led to discontinuation. Single- and multiple-dose PKs of ODN 50 mg in Chinese postmenopausal women were generally similar to those previously reported in non-Chinese postmenopausal women.
odanacatib（ODN）是一种口服的组织蛋白酶 K 选择性抑制剂，之前是作为骨质疏松症治疗药物进行研发的。在这项 1 期、开放标签的研究中，12 名健康的绝经后中国女性在禁食条件下于第 1 天接受单次剂量的 ODN 50mg，第 15、22、29 和 36 天接受多次剂量的 ODN 50mg，每周一次。在第 1 天和第 36 天评估药代动力学（PK）参数。比较单次和多次剂量后的曲线下面积（AUC）和最大血浆浓度（C ）与 9 名非中国绝经后女性的历史数据，这些女性也接受了 ODN 50mg 每周一次，共 4 周。单次和多次给药后 C 的中位数达峰时间（t ）分别为 3 小时和 4 小时。单次和多次给药后的算术平均值±标准差终末半衰期分别为 81.0±14.0 小时和 106.7±14.4 小时。多次剂量 PK 参数比较显示，AUC 和 C 的几何均数比值（中国人/非中国人）及其 95%置信区间分别为 0.81（0.55-1.19）和 0.87（0.69-1.11）。所有不良事件均为轻度，无严重不良事件，也无任何不良事件导致停药。ODN 50mg 在中国绝经后女性中的单次和多次剂量 PK 与之前在非中国绝经后女性中的报告基本相似。
