Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Acta Pharmacol Sin. 2011 Dec;32(12):1555-60. doi: 10.1038/aps.2011.138. Epub 2011 Oct 10.
To evaluate the pharmacokinetics of L-threonate after single or multiple oral administrations and its safety profile in healthy Chinese volunteers.
This was an open-label, single- and multiple-dose study. The subjects were assigned to receive a single dose, 675, 2025, or 4050 mg, of calcium L-threonate (n=12) or repeated doses of 2025 mg twice daily for 4 d (n=12). Serial plasma and urine samples were analyzed with HPLC-MS/MS. Pharmacokinetic parameters of L-threonate were calculated using non-compartmental analysis with WinNonlin software.
In the single dose group, C(max) reached at 2.0 h and the mean t(1/2) was approximately 2.5 h. Area under curve (AUC) and C(max) increased with dose escalation, but dose proportionality was not observed over the range of 675 to 4050 mg. AUC and C(max) in the fasted subjects were lower compared with those in the non-fasted subjects. Cumulative urinary excretion of L-threonate over 24 h represented 5.9% of the administered dose with a mean Cl/r of 0.8 L/h. In the multiple-dose study, no accumulation appeared upon repeated doses of 2025 mg twice daily for 4 d. There were no serious adverse events that occurred during this study.
Calcium L-threonate was well tolerated in healthy Chinese subjects, with no pattern of dose-related adverse events. Plasma exposure increased with dose escalation, but linear pharmacokinetics were not observed over the studied doses. L-threonate was absorbed rapidly, and its absorption was enhanced by food intake. No systemic accumulation appeared after repeated administrations.
评估单剂和多剂口服 L-苏糖酸钙后的药代动力学特征及其在健康中国志愿者中的安全性。
这是一项开放标签、单剂量和多剂量研究。受试者被分配接受单剂量 675、2025 或 4050 mg 的 L-苏糖酸钙（n=12）或重复剂量 2025 mg，每日两次，连续 4 天（n=12）。采用 HPLC-MS/MS 分析连续的血浆和尿液样本。使用非房室分析和 WinNonlin 软件计算 L-苏糖酸钙的药代动力学参数。
在单剂量组中，C(max)在 2.0 小时达到，平均 t(1/2)约为 2.5 小时。AUC 和 C(max)随剂量增加而增加，但在 675 至 4050 mg 范围内未观察到剂量比例性。空腹受试者的 AUC 和 C(max)低于非空腹受试者。24 小时内 L-苏糖酸钙的累积尿液排泄量占给药剂量的 5.9%，平均 Cl/r 为 0.8 L/h。在多剂量研究中，连续 4 天每日两次给予 2025 mg 时未出现重复剂量的蓄积。研究期间未发生严重不良事件。
L-苏糖酸钙在中国健康受试者中耐受良好，无剂量相关不良事件模式。血浆暴露随剂量增加而增加，但在研究剂量范围内未观察到线性药代动力学。L-苏糖酸钙吸收迅速，食物摄入可增强其吸收。重复给药后未出现全身蓄积。
