title: Pharmacokinetics and safety of calcium L-threonate in healthy volunteers after single and multiple oral administrations.
abstract: OBJECTIVE
  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, 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.
  
  
  CONCLUSIONS
  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.
authors: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors: Hong-yun
authors: HY
authors: Wang
authors: Pei
authors: P
authors: Hu
authors: Ji
authors: J
authors: Jiang
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002087:Butyrates / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D012016:Reference Values; D053719:Tandem Mass Spectrometry
chemical_list: D002087:Butyrates; C011369:threonic acid