European Journal of Clinical Pharmacology

, Volume 69, Issue 5, pp 1121–1126 | Cite as

Calcium bioavailability of calcium L-threonate in healthy Chinese subjects measured with stable isotopes (44Ca and 42Ca)

Pharmacokinetics and Disposition



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.


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.


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.


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.


Calcium bioavailability Stable isotopes Calcium L-threonate Chinese 


  1. 1.
    Cooper C, Campion G, Melton LJ 3rd (1992) Hip fractures in the elderly: a world-wide projection. Osteoporos Int 2:285–289PubMedCrossRefGoogle Scholar
  2. 2.
    Sambrook P, Cooper C (2006) Osteoporosis. Lancet 367:2010–2018PubMedCrossRefGoogle Scholar
  3. 3.
    Nickel KP, Martin BR, Smith DL, Smith JB, Miller GD, Weaver CM (1996) Calcium bioavailability from bovine milk and dairy products in premenopausal women using intrinsic and extrinsic labeling techniques. J Nutr 126:1406–1411PubMedGoogle Scholar
  4. 4.
    Teucher B, Dainty JR, Fairweather-Tait SJ (2001) Original communication high bioavailability of calcium in forti®ed Horlicks. Eur J Clin Nutr 55:778–781PubMedCrossRefGoogle Scholar
  5. 5.
    Zhao Y, Martin BR, Weaver CM (2005) Calcium bioavailabilityof calcium carbonate fortified soymilk is equivalent to cow’s milk in young women. J Nutr 135:2379–2382PubMedGoogle Scholar
  6. 6.
    Heaney RP, Dowell MS, Rafferty K, Bierman J (2000) Bioavailability of the calcium in fortified soy imitation milk, with some observations on method. Am J Clin Nutr 71:1166–1169PubMedGoogle Scholar
  7. 7.
    Fairweather-Tait SJ, Johnson A, Eagles J, Ganatra S, Kennedy H, Gurr MI (1989) Studies on calcium absorption from milk using a double-label stable isotope technique. Br J Nutr 62(2):379–388PubMedCrossRefGoogle Scholar
  8. 8.
    Hillman LS (2011) Use of the dual stable isotope method to assess calcium absorption and retention in premature infants. J Pediatr 158:876–877PubMedCrossRefGoogle Scholar
  9. 9.
    Ceglia L, Abrams SA, Harris SS, Rasmussen HM, Dallal GE, Dawson-Hughes B (2010) A simple single serum method to measure fractional calcium absorption using dual stable isotopes. Exp Clin Endocrinol Diabetes 118:653–656PubMedCrossRefGoogle Scholar
  10. 10.
    Lee WT, Leung SS, Fairweather-Tait SJ, Leung DM, Tsang HS, Eagles J, Fox T, Wang SH, Xu YC, Zeng WP (1994) True fractional calcium absorption in Chinese children measured with stable isotopes (42Ca and 44Ca). Br J Nutr 72:883–897PubMedCrossRefGoogle Scholar
  11. 11.
    Lee WT, Leung SS, Lui SS, Lau J (1993) Relationship between long-term calcium intake and bone mineral content of children aged from birth to 5 years. Br J Nutr 70:235–248PubMedCrossRefGoogle Scholar
  12. 12.
    Hillman LS, Tack E, Covell DG, Vieria NE, Al Y (1988) Measurement of true calcium absorption in premature infants using intravenous 46Ca and oral 44Ca. Pediatr Res 23:589–594PubMedCrossRefGoogle Scholar
  13. 13.
    Chen YM, Teucher B, Tang XY, Dainty JR, Lee KK, Woo JL, Ho SC (2007) Calcium absorption in postmenopausal Chinese women: a randomized crossover intervention study. Br J Nutr 97:160–166PubMedCrossRefGoogle Scholar
  14. 14.
    Lee WT, Jiang J, Hu P, Hu X, Roberts DC, Cheng JC (2002) Use of stable calcium isotopes (42Ca & 44Ca) in evaluation of calcium absorption in Beijing adolescents with low vitamin D status. Food Nutr Bull 23:42–47PubMedGoogle Scholar
  15. 15.
    Wang HY, Hu P, Jiang J (2011) Pharmacokinetics and safety of calcium L-threonate in healthy volunteers after single and multiple oral administrations. Acta Pharmacol Sin 32:1555–1560PubMedCrossRefGoogle Scholar
  16. 16.
    Patterson KY, Veillon C, Hill DA, Moser-Veillon PB, O’Haver TC (1999) Measurement of calcium stable isotope tracers using cool plasma ICP-MS. J Anal Atom Spectrom 14:1673–1677CrossRefGoogle Scholar
  17. 17.
    Turnlund JR, Keyes WR, Scott KC (1993) Isotope ratios of calcium determined in calcium-46 enriched samples from infants by automated multiple-collector thermal ionization mass spectrometry. J Anal Atom Spectrom 8:983–987CrossRefGoogle Scholar
  18. 18.
    Yergey AL, Vieira NE, Covell DG (1987) Direct measurement of dietary functional absorption using calcium isotopic tracers. Biomed Environ Mass Spectrom 14:603–607PubMedCrossRefGoogle Scholar
  19. 19.
    Eastell R, Visria NE, Yergey AL, Riggs L (1989) One-day test using stable isotopes to measure true fractional calcium absorption. J Bone Miner Res 4:463–468PubMedCrossRefGoogle Scholar
  20. 20.
    Smith DL, Atkin C, Westenfelder C (1985) Stable isotopes of calcium as tracers:methodology. Clin Chim Acta 146:97–101PubMedCrossRefGoogle Scholar
  21. 21.
    Yergey AL, Abrams SA, Vieira NE, Eastell R, Hillman LS, Covell DG (1990) Recent studies of human calcium metabolism using stable isotopic tracer. Can J Physiol Pharmacol 68:973–976PubMedCrossRefGoogle Scholar
  22. 22.
    Fairweather-Tait S, Prentice A, Heumann KG, Jarjou LM, Stirling DM, Wharf SG, Turnlund JR (1995) Effect of calcium supplements and stage of lactation on the calcium absorption efficiency of lactating women accustomed to low calcium intakes. Am J Clin Nutr 62:1188–1192PubMedGoogle Scholar
  23. 23.
    Fields MP, Shapses S, Cifuentes M, Sherrell RM (2003) Precise and accurate determination of calcium isotope ratios in urine using HR-ICP-SFMS. J Anal Atomic Spectrom 18:727–733CrossRefGoogle Scholar
  24. 24.
    Smith DL (1983) Determination of stable isotopes of calcium in biological fluids by fast atom bombardment mass spectrometry. Anal Chem 55:2391–2393PubMedCrossRefGoogle Scholar
  25. 25.
    Jiang X, Smith DL (1987) Quantitation of stable isotopic tracer of calcium by fast atom bombardment mass spectrometry. Anal Chem 59:2570–2574PubMedCrossRefGoogle Scholar
  26. 26.
    Kayganich-Harrison KA, Murphy RC (1994) Incorporation of stable isotope-labeled arachidonic acid into cellular phospholipid molecular species and analysis by fast atom bombardment tandem mass spectrometry. Biol Mass Spectrom 23:562–571PubMedCrossRefGoogle Scholar
  27. 27.
    Yergey AL (1996) Analytical instruments for stable isotopic tracers in mineral metabolism. J Nutr 126:355–356Google Scholar
  28. 28.
    Yergey AL, Vieira NE, Hansen JW (1980) Isotope ratio measurements of urinary calcium with a Thermal Ionization probe in a quadrupole mass spectrometer. Anal Chem 52:1811–1814PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Clinical Pharmacology Research CenterPeking Union Medical College HospitalBeijingPeople’s Republic of China

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