Advertisement

Ocular Pharmacokinetics of 25-Hydroxyvitamin D3 After Weekly Supplementation in Rabbits Using Ultra Performance Liquid Chromatography–Tandem Mass Spectrometer

  • Archit Kumar
  • Mini P. Singh
  • Tripti Rungta
  • Ajay Patial
  • Savita Verma Attri
  • Bikash Medhi
  • Radha Kanta Ratho
Short Communication

Abstract

Background and Objectives

The protective role of vitamin D supplementation has recently been shown to be present in various ocular inflammatory diseases. The oral supplementation of vitamin D may take time to achieve adequate levels in intraocular fluids. Therefore, the present study was performed to understand the ocular pharmacokinetics of 25-hydroxyvitamin D3 (25D3) in aqueous humor after weekly supplementation of 25D3 in rabbits.

Methods

A total of 21 rabbits were fed orally with 25D3 (7.22 µg/kg/week) for 8 weeks and 9th dose was given at the end of 8 weeks. The blood and aqueous humor samples were collected from ear vein and though anterior chamber paracentesis, respectively. The serum and aqueous humor samples were spiked with deuterium labeled internal standard and were extracted using liquid extraction method. Furthermore, the samples were derivatized and 25D3 estimation was performed using ultra performance liquid chromatography–tandem mass spectrometer (UHPLC–MS/MS).

Results

The 25D3 supplementation significantly increased the 25D3 levels in serum (78.5 ± 21.6 ng/ml) (mean ± SD) (p < 0.0001) and in aqueous humor (991.3 ± 180.6 pg/ml) (mean ± SD) (p < 0.0001) compared to baseline levels. The maximum concentration was achieved in serum after the 10th hour of supplementation of 1st and 9th dose, while the same was observed at the 24th hour in aqueous humor.

Conclusion

The oral supplementation of 25D3 was found to significantly increase 25D3 levels in aqueous humor; however, the time required to achieve 25D3 concentration in aqueous humor was higher as compared to that in serum. Therefore, weekly oral supplementation of 25D3 may have a beneficial role in ocular diseases.

Notes

Acknowledgements

We thank Shefali Saini for her assistance in experiments when required.

Author Contributions

AK, MPS and BM conceived the idea and planned the study design. The experiments were performed by AK. The LCMS were performed by AP and AK. TR assisted during animal experiments and LCMS. The paper was drafted by AK and MPS and critically reviewed by SV, BM and RKR.

Compliance with ethical standards

Conflict of interest

The authors have declared no conflict of interest.

Ethical approval

The animal experimentations were performed after obtaining animal ethical clearance from Institute Animal Ethics Committee (Reference No. IAEC-66/IAEC/396).

Funding

The study was funded by Department of Biotechnology, New Delhi Reference No. BT/PR10811/MED/29/840/2014.

References

  1. 1.
    Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.CrossRefPubMedGoogle Scholar
  2. 2.
    Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017;18:153–65.CrossRefPubMedGoogle Scholar
  3. 3.
    Ozkan B, Hatun S, Bereket A. Vitamin D intoxication. Turk J Pediatr. 2012;54:93–8.PubMedGoogle Scholar
  4. 4.
    Gupta A. Vitamin D deficiency in India: prevalence, causalities and interventions. Nutrients. 2014;6:729–75.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Banerjee A, Khemka VK, Roy D, Dhar A, Sinha Roy TK, Biswas A, et al. Role of pro-inflammatory cytokines and vitamin D in probable Alzheimer’s disease with depression. Aging Dis. 2017;8:267–76.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Beard JA, Bearden A, Striker R. Vitamin D and the anti-viral state. J Clin Virol. 2011;50:194–200.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Buondonno I, Rovera G, Sassi F, Rigoni MM, Lomater C, Parisi S, et al. Vitamin D and immunomodulation in early rheumatoid arthritis: a randomized double-blind placebo-controlled study. PLoS One. 2017;12:e0178463.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Gutierrez JA, Parikh N, Branch AD. Classical and emerging roles of vitamin D in hepatitis C virus infection. Semin Liver Dis. 2011;31:87–98.CrossRefGoogle Scholar
  9. 9.
    Gutierrez JA, Jones KA, Flores R, Singhania A, Woelk CH, Schooley RT, et al. Vitamin D metabolites inhibit hepatitis C virus and modulate cellular gene expression. J Virol Antivir Res. 2014;3.Google Scholar
  10. 10.
    Limketkai BN, Mullin GE, Limsui D, Parian AM. Role of vitamin D in inflammatory bowel disease. Nutr Clin Pract. 2017;32:337–45.CrossRefPubMedGoogle Scholar
  11. 11.
    FDA 2016. Vitamin D for Milk and Milk Alternatives 2016. https://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm510522.htm. Accessed 30 July 2017.
  12. 12.
    Cashman KD, Seamans KM, Lucey AJ, Stöcklin E, Weber P, Kiely M, et al. Relative effectiveness of oral 25-hydroxyvitamin D3 and vitamin D3 in raising wintertime serum 25-hydroxyvitamin D in older adults. Am J Clin Nutr. 2012;95:1350–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Jetter A, Egli A, Dawson-Hughes B, Staehelin HB, Stoecklin E, Goessl R, et al. Pharmacokinetics of oral vitamin D3 and calcifediol. Bone. 2014;59:14–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Haddad JG, Rojanasathit S. Acute administration of 25-hydroxycholecalciferol in man. J Clin Endocrinol Metab. 1976;42:284–90.CrossRefPubMedGoogle Scholar
  15. 15.
    Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008;88:582S–6S.CrossRefPubMedGoogle Scholar
  16. 16.
    Ketha H, Wadams H, Lteif A, Singh RJ. Iatrogenic vitamin D toxicity in an infant—a case report and review of literature. J Steroid Biochem Mol Biol. 2015;148:14–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Lee V, Rekhi E, Kam JH, Jeffery G. Vitamin D rejuvenates aging eyes by reducing inflammation, clearing amyloid beta and improving visual function. Neurobiol Aging. 2012;33:2382–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Mutti DO, Marks AR. Blood levels of vitamin D in teens and young adults with myopia. Optom Vis Sci. 2011;88:377–82.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol. 2007;125:661–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Payne JF, Ray R, Watson DG, Delille C, Rimler E, Cleveland J, et al. Vitamin D insufficiency in diabetic retinopathy. Endocr Pract. 2012;18:185–93.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sabet SJ, Darjatmoko SR, Lindstrom MJ, Albert DM. Antineoplastic effect and toxicity of 1,25-dihydroxy-16-ene-23-yne-vitamin D3 in athymic mice with Y-79 human retinoblastoma tumors. Arch Ophthalmol. 1999;117:365–70.CrossRefPubMedGoogle Scholar
  22. 22.
    Tang J, Zhou R, Luger D, Zhu W, Silver PB, Grajewski RS, et al. Calcitriol suppresses antiretinal autoimmunity through inhibitory effects on the Th17 effector response. J Immunol. 2009;182:4624–32.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Millen AE, Meyers KJ, Liu Z, Engelman CD, Wallace RB, LeBlanc ES, et al. Association between vitamin D status and age-related macular degeneration by genetic risk. JAMA Ophthalmol. 2015;133:1171–9.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Yoon SY, Bae SH, Shin YJ, Park SG, Hwang SH, Hyon JY, et al. Low serum 25-hydroxyvitamin D levels are associated with dry eye syndrome. PLoS One. 2016;11:e0147847.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Bae SH, Shin YJ, Kim HK, Hyon JY, Wee WR, Park SG. Vitamin D supplementation for patients with dry eye syndrome refractory to conventional treatment. Sci Rep. 2016;6:33083.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    NCT00718276. Pharmacokinetic Study: Effect of 25(OH)D and vitamin D3 on serum 25(OH)D—Full Text View—ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT00718276. Accessed 30 July 2017.
  27. 27.
    Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7:27–31.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ding S, Schoenmakers I, Jones K, Koulman A, Prentice A, Volmer DA. Quantitative determination of vitamin D metabolites in plasma using UHPLC–MS/MS. Anal Bioanal Chem. 2010;398:779–89.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Enko D, Kriegshäuser G, Stolba R, Worf E, Halwachs-Baumann G. Method evaluation study of a new generation of vitamin D assays. Biochem Med. 2015;25:203–12.CrossRefGoogle Scholar
  30. 30.
    He CS, Gleeson M, Fraser WD. Measurement of circulating 25-hydroxy vitamin d using three commercial enzyme-linked immunosorbent assay kits with comparison to liquid chromatography: tandem mass spectrometry method. ISRN Nutr. 2013;2013:723139.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Lou YR, Molnár F, Peräkylä M, Qiao S, Kalueff AV, St-Arnaud R, et al. 25-Hydroxyvitamin D(3) is an agonistic vitamin D receptor ligand. J Steroid Biochem Mol Biol. 2010;118:162–70.CrossRefPubMedGoogle Scholar
  32. 32.
    Lin Y, Ubels JL, Schotanus MP, Yin Z, Pintea V, Hammock BD, et al. Enhancement of vitamin D metabolites in the eye following vitamin D3 supplementation and UV-B irradiation. Curr Eye Res. 2012;37:871–8.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Brommage R, Miller SC, Langman CB, Bouillon R, Smith R, Bourdeau JE. The effects of chronic vitamin D deficiency on the skeleton in the adult rabbit. Bone. 1988;9:131–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Emerson JA, Whittington JK, Allender MC, Mitchell MA. Effects of ultraviolet radiation produced from artificial lights on serum 25-hydroxyvitamin D concentration in captive domestic rabbits (Oryctolagus cuniculi). Am J Vet Res. 2014;75:380–4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of VirologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  2. 2.Advanced Pediatrics CentrePostgraduate Institute of Medical Education and ResearchChandigarhIndia
  3. 3.Department of PharmacologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia

Personalised recommendations