Multidirectional vector pathways of vitamin D metabolism as modifiers of its interaction with drugs

O.M. Nikolova, O.A. Yakovleva


Background. The comorbid pathology characteristic of the elderly and senile people may lead to polypharmacy. The leading role in the metabolism of drugs is played by the cytochrome (CY) P450 system. The use of vitamin D in geriatric patients is of particular importance taking into account their age-specific features of metabolism. The purpose of the review was to analyse the international contemporary information content on the interaction of vitamin D with the system of metabolism of the drugs. Materials and methods. Analysis of American and European scientific sources was performed. Results. More than 11,500 proteins of the CYP system are currently described. In the metabolism of medicines, the following six are involved: CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP2E1, CYP3A4, which provide biotransformation of drugs through oxidation. CYP450 is a hemoprotein that provides binding of the substrate molecules with activation of oxygens, resulting in the formation of oxidation, a more hydrophilic product and water molecule. The insufficiency of hydroxylation capacity of the liver and kidneys can lead to D-hypovitaminosis in the body of patients. CYP11A1, СYР27А1, СYР27В1, СYР24А1 are responsible for vitamin D metabolism. Conducted studies have shown that these cytochromes metabolize a number of other drugs that can act as their inhibitors and inducers. Conclusions. The system of cytochrome P450 influences the formation of vitamin D metabolites. Taking into account the physiological ways of its metabolism, multidirectional results of interaction are formed.


cytochrome P450; vitamin D; interaction; meta­bolism


Anisimova SI, Shayakhmetova SI, Bondarenko LB. Hepatotoxicity of a combination of anti-tuberculosis agents of the I series, caused by modulation of the expression of cytochromes P450 2E1, 2C23 and 3A2 in the liver of white rats. Farmakologija ta likars'ka toksykologija. 2011;5:12-14. (In Ukrainian).

Belcher J, McLean KJ, Matthews S, et al. Structure and biochemical properties of the alkene producing cytochrome P450 OleTJE (CYP152L1) from the Jeotgalicoccus sp. 8456 bacterium. J Biol Chem. 2014 Mar 7;289(10):6535-50. doi: 10.1074/jbc.M113.527325.

Quack Lötscher KC, l'Allemand D, Bischoff-Ferrari HA, Burckhardt P. Vitamin D deficiency: Evidence, safety, and recommendations for the Swiss population. Zurich: Federal Office of Public Health; 2012. 95 p.

Farrell C.J., Herrmann M. Determination of vitamin D and its metabolites. Best Pract Res Clin Endocrinol Metab. 2013 Oct;27(5):675-88. doi: 10.1016/j.beem.2013.06.001.

Gandhi S, Fleet JL, Bailey DG, et al. Cаlcium-channel blocker-clarithrovecin dru interactions and acute kidney injury. JAMA. 2013 Dec 18;310(23):2544-53. doi: 10.1001/jama.2013.282426.

Goodman LS, Limbrid LE, Gilman A, et al. Goodman & Gilman's The pharmacological basis of therapeutics. Sydney : McGraw-Hill Health Professions Division; 1996. 1905 p.

Hermann M, Scholmerich J, Straub R. Influence of cytokines and growth factors on distinct steroidogenic enzymes in vitro: a short tabular data collection. Ann N Y Acad Sci. 2002 Jun;966:166-86.

Holick MF. Vitamin D: extraskeletal health. Rheum Dis Clin North Am. 2012 Feb;38(1):141-60. doi: 10.1016/j.rdc.2012.03.013.

Hossein-nezhad A, Holick MF. Optimize dietary intake of vitamin D: an epigenetic perspective. Curr Opin Clin Nutr Metab Care. 2012 Nov;15(6):567-79. doi: 10.1097/MCO.0b013e3283594978.

Komisarenko YI. Study of the effects of vitamin E on vitamin D3, mineral and carbohydrate metabolism in experimental diabetes mellitus. Endocrynologia. 2012;17(1):61-64. (in Ukrainian).

Komisarenko YI. Vitamin D and its Role in the Regulation of Metabolic Disorders in Diabetes Mellitus. Liky Ukrai'ny. 2013;(4):51-54. (In Ukrainian).

Khomenko AV. Cholecalciferol hydroxylation in rat hepatocytes under the influence of prednisolone. Ukrainian Biochemical Journal. 2013;85(3):90-95. (in Ukrainian).

Maidannik VG. Klinicheskie rekomendatsii po diagnostike, lecheniiu i profilaktike vitamin D-defitsitnogo rakhita u detei [Clinical recommendations for the diagnosis, treatment and prevention of vitamin D-deficiency rickets in children]. Kyiv; 2014. 58 p. (in Russian).

Mazzaferro S, Goldsmith D, Larsson TE, Massy ZA, Cozzolino M. Vitamin D metabolites and/or analogs: which D for which patient? Curr Vasc Pharmacol. 2014 Mar;12(2):339-49.

Mestres J. Structure conservation in cytochromes P450. Proteins. 2005 Feb 15;58(3):596-609. doi: 10.1002/prot.20354.

Nebert DW, Wikvall K, Miller WL. Human cytochromes P450 in health and disease. Philos Trans R Soc Lond B Biol Sci. 2013 Jan 6;368(1612):20120431. doi: 10.1098/rstb.2012.0431.

Parekh AK, Kronick R, Tavenner M. Optimizing health for persons with multiple chronic conditions. JAMA. 2014 Sep 24;312(12):1199-200. doi: 10.1001/jama.2014.10181.

Povoroznyuk VV, Balatska NI. Vitamin D Deficiency in the Population of Ukraine and the Risk Factors for its Development. Bolʹ, sustavy, pozvonočnik. 2012;(8):5-11. (in Ukrainian).

Saraf R, Morton SM, Camargo CA Jr, Grant CC. Global summary of maternal and newborn vitamin D status - a systematic review. Matern Child Nutr. 2016 Oct;12(4):647-68. doi: 10.1111/mcn.12210.

Slominski AT, Kim TK, Li W, Yi AK, Postlethwaite A, Tuckey RC. The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions. J Steroid Biochem Mol Biol. 2014 Oct;144 Pt A:28-39. doi: 10.1016/j.jsbmb.2013.10.012.

Sørnes S, Bjøro T, Berg JP, Torjesen PA, Haug E. Calcitriol attenuates the basal and vasoactive intestinal peptide-stimulated cAMP production in prolactin-secreting rat pituitary (GH4C1) cells. Mol Cell Endocrinol. 1994 May;101(1-2):183-8.

Semin SG, Volkova LV, Moiseev AB, Nikitina NV. Prospects for the study of the biological role of vitamin D. Pediatria. 2012;91(2):122-131. (in Russian).

Spirichev VB. About biological effects of vitamin D. Pediatria. 2011;90(6):113-119. (in Russian).

Singh RJ, Taylor RL, Reddy GS, Grebe SK. C-3 epimers can account for a significant proportion of total circulating 25-hydroxyvitamin D in infants, complicating accurate measurement and interpretation of vitamin D status. J Clin Endocrinol Metab. 2006 Aug;91(8):3055-61. doi: 10.1210/jc.2006-0710.

Wehr E, Trummer O, Giuliani A, Gruber HJ, Pieber TR, Obermayer-Pietsch B. Vitamin D associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol. 2011 May;164(5):741-9. doi: 10.1530/EJE-11-0134.

Yip YL, Famiglietti M, Gos A, at al. Annotating single amino acid polymorphisms in the UniProt/Swiss-Prot knowledgebase. Hum Mutat. 2008 Mar;29(3):361-6. doi: 10.1002/humu.20671.

Copyright (c) 2020 O.M. Nikolova, O.A. Yakovleva

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© Publishing House Zaslavsky, 1997-2020


   Seo анализ сайта