Pharmacokinetics and safety of calcium L-threonate in healthy volunteers after single and multiple oral administrations

Aim: To evaluate the pharmacokinetics of L-threonate after single or multiple oral administrations and its safety profile in healthy Chinese volunteers. Methods: 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 ca...

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Veröffentlicht in:Acta pharmacologica Sinica 2011-12, Vol.32 (12), p.1555-1560
Hauptverfasser: Wang, Hong-yun, Hu, Pei, Jiang, Ji
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Sprache:eng
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Zusammenfassung:Aim: To evaluate the pharmacokinetics of L-threonate after single or multiple oral administrations and its safety profile in healthy Chinese volunteers. Methods: 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. Results: In the single dose group, Cmax reached at 2.0 h and the mean t1/2 was approximately 2.5 h. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 675 to 4050 mg. AUC and Cmax 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 CI/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. Conclusion: 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.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2011.138