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

Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Acta Pharmacologica Sinica (Impact Factor: 2.91). 12/2011; 32(12):1555-60. DOI: 10.1038/aps.2011.138
Source: PubMed


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.

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Available from: Pei Hu, Jun 18, 2014
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    ABSTRACT: Purpose Calcium L-threonate is a novel drug that was developed for the treatment of osteoporosis and as a calcium supplement. However, calcium bioavailability of this drug is unknown due to lack of effective evaluation methods. In this study, we sought to measure the bioavailability of calcium L-threonate with a double-label stable isotope method. Methods Fourteen healthy Chinese subjects were enrolled in the clinical study and were given 300 mg calcium L-threonate tablets containing 40 mg 44Ca after an intravenous injection of 4 mg 42Ca solution (as calcium chloride). Fractional urine samples were collected at the following time intervals: 0–3, 3–6, 6–9, 9–13, 13–24, 24–36 and 36–48 h. The abundance ratios of 44Ca/40Ca and 42Ca/40Ca in the urine were determined with thermal-ionization mass spectrometry (TI-MS). The calcium bioavailability was estimated by calculating the true fractional calcium absorption (TFCA) using the abundance ratios of 44Ca/40Ca and 42Ca/40Ca. Results The bioavailability of calcium L-threonate in 14 healthy Chinese subjects was 26.49 ± 9.39 %. There was good agreement between TFCA from the 24 to 36 h and the 36 to 48 h urine pool, indicating that calcium balance was achieved at 24 h after dosing. The TFCA of the subjects did not statistically correlate with total urinary calcium excretion (0–48 h). There were no serious adverse events in this study. Conclusions The bioavailability of calcium L-threonate in humans was successfully determined by estimating TFCA with the double-label stable isotope method, thus providing a useful approach for the evaluation of bioavailability of calcium formulations.
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