Skip to main content
SpringerLink
Log in

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

  • Short Communication
  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.

    Article  PubMed  CAS  Google Scholar 

  2. Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017;18:153–65.

    Article  PubMed  CAS  Google Scholar 

  3. Ozkan B, Hatun S, Bereket A. Vitamin D intoxication. Turk J Pediatr. 2012;54:93–8.

    PubMed  Google Scholar 

  4. Gupta A. Vitamin D deficiency in India: prevalence, causalities and interventions. Nutrients. 2014;6:729–75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Beard JA, Bearden A, Striker R. Vitamin D and the anti-viral state. J Clin Virol. 2011;50:194–200.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

  10. Limketkai BN, Mullin GE, Limsui D, Parian AM. Role of vitamin D in inflammatory bowel disease. Nutr Clin Pract. 2017;32:337–45.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  14. Haddad JG, Rojanasathit S. Acute administration of 25-hydroxycholecalciferol in man. J Clin Endocrinol Metab. 1976;42:284–90.

    Article  PubMed  CAS  Google Scholar 

  15. Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008;88:582S–6S.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  18. Mutti DO, Marks AR. Blood levels of vitamin D in teens and young adults with myopia. Optom Vis Sci. 2011;88:377–82.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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. Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7:27–31.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

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

Author information

Authors and Affiliations

  1. Department of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Archit Kumar, Mini P. Singh, Tripti Rungta & Radha Kanta Ratho

  2. Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Ajay Patial & Savita Verma Attri

  3. Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Bikash Medhi

Authors
  1. Archit Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mini P. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tripti Rungta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ajay Patial
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Savita Verma Attri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bikash Medhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Radha Kanta Ratho
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Corresponding author

Correspondence to Mini P. Singh.

Ethics declarations

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, A., Singh, M.P., Rungta, T. et al. Ocular Pharmacokinetics of 25-Hydroxyvitamin D3 After Weekly Supplementation in Rabbits Using Ultra Performance Liquid Chromatography–Tandem Mass Spectrometer. Eur J Drug Metab Pharmacokinet 43, 607–613 (2018). https://doi.org/10.1007/s13318-018-0470-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13318-018-0470-1

Search

Navigation