Vitamin D

Identification

Summary

Vitamin D is an ingredient found in a variety of supplements and vitamins.

Brand Names

Mvc-fluoride, Vitafol-one

Generic Name

Vitamin D

DrugBank Accession Number

DB11094

Background

Vitamin D ultimately comprises a group of lipid-soluble secosteroids responsible for a variety of biological effects, some of which include increasing the intestinal absorption of calcium, magnesium, and phosphate. With reference to human use, there are 2 main forms of vitamin D - vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). When non-specific references are made about 'vitamin d', the references are usually about the use of vitamin D3 and/or D2.

Vitamin D3 and D2 require hydroxylation in order to become biologically active in the human body. Since vitamin D can be endogenously synthesized in adequate amounts by most mammals exposed to sufficient quantities of sunlight, vitamin D functions like a hormone on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Vitamin D plays an essential physiological role in maintaining calcium homeostasis and metabolism. There are several different vitamin D supplements that are given to treat or to prevent osteomalacia and rickets, or to meet the daily criteria of vitamin D consumption.

Type

Small Molecule

Groups

Approved, Nutraceutical, Vet approved

Synonyms

• Calciferol
• Vitamin D NOS
• Vitamin D, unspecified form

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Pharmacology

Indication

Vitamin D is indicated for use in the treatment of hypoparathyroidism, refractory rickets (also known as vitamin D resistant rickets), and familial hypophosphatemia ^Label.

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Used in combination to prevent	Deficiency, vitamin d	Combination Product in combination with: Cholecalciferol (DB00169)	••••••••••••			•••••••• • •••••
Used in combination to treat	Deficiency, vitamin d	Combination Product in combination with: Cholecalciferol (DB00169)	••••••••••••			•••••••• • •••••
Prevention of	Deficiency, vitamin d		••• •••

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Pharmacodynamics

The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 or D2 occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D ^Label. These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization ^Label. Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules ^Label. There exists a period of 10 to 24 hours between the administration of vitamin D and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys ^Label. It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys ^Label.

Mechanism of action

Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight.²

Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease ¹. Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone ². Increases in parathyroid hormone stimulates the mobilization of skeletal calcium and the renal excretion of phosphorus ². This enhanced mobilization of skeletal calcium leads towards porotic bone conditions ².

Ordinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet ². At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation ^2,1. This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma ^2,1.

Target	Actions	Organism
UVitamin D3 receptor	Not Available	Humans
UVitamin D-binding protein	Not Available	Humans

Absorption

Vitamin D3 and D2 are readily absorbed from the small intestine (proximal or distal) ^2,1.

Volume of distribution

Not Available

Protein binding

Some studies suggest vitamin D3 demonstrates protein binding of 50-80% ¹ while others discuss vitamin D2 having >99.8% protein binding ².

Metabolism

In the liver, vitamin D3 and D2 are hydroxylated to calcidiol (25-hydroxycholecalciferol) ¹ and ercalcidiol (25-hydroxyergocalciferol) ², respectively, by the enzyme 25-hydroxylase. At the level of the kidney, calcidiol and ercalcidiol are hydroxylated to yield calcitriol (1,25-dihydroxycholecalciferol) ¹ and ercalcitriol (1,25-dihydroxyergocalciferol) ², the primary biologically active forms of vitamin D3 and D2 respectively, by the enzyme 1-alpha-hydroxylase.

Hover over products below to view reaction partners

• Vitamin D
  • Calcifediol
    • Calcitriol
  • 25-Hydroxyvitamin D2-25-glucuronide
    • 25-Hydroxyvitamin D2 25-(beta-glucuronide)

Route of elimination

The primary excretion route of vitamin D is via the bile into the feces ³.

Half-life

Although certain studies suggest the half-life of 1,25-hydroxyvitamin D3 may be approximately 15 hours, the half-life of 25-hydroxyvitamin D3 appears to have a half-life of about 15 days ⁶. Intriguingly however, the half-lives of any particular administration of vitamin d can vary and in general the half-lives of vitamin D2 metabolites have been demonstrated to be shorter overall than vitamin D3 half-lives with this being affected by vitamin d binding protein concentrations and genotype in particular individuals ⁴.

Clearance

Some studies propose an estimated clearance rate for 1,25-dihydroxyvitamin D as 31 +/- 4 ml/min in healthy adults ⁵.

Adverse Effects

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Toxicity

The use of pharmacological or nutraceutical vitamin d and/or even excessive dietary intake of vitamin d is contraindicated in patients with hypercalcemia, malabsorption syndrome, abnormal sensitivity to the toxic effects of vitamin d, and hypervitaminosis D ^Label.

Hypersensitivity to vitamin d is one plausible etiologic factor in infants with idiopathic hypercalcemia - a case in which vitamin d use must be strictly restricted ^Label.

As vitamin d intake is available via fortified foods, dietary supplements, and clinical drug sources, serum concentrations and therapeutic dosages should be reviewed regularly and readjusted as soon as there is clinical improvement ^Label. Dosage levels are required to be individualized on an individual patient by patient basis as caution must be exercised to prevent the presence of too much vitamin d in the body and the various potentially serious toxic effects associated with such circumstances ^Label.

In particular, the range between therapeutic and toxic doses is quite narrow in vitamin d resistant rickets ^Label. When high therapeutic doses are used, progress should be followed with frequent blood calcium determinations ^Label.

When treating hypoparathyroidism, intravenous calcium, parathyroid hormone, and/or dihydrotachysterol may be required ^Label.

Maintenance of normal serum phosphorus levels by dietary phosphate restriction and/or administration of aluminum gels as intestinal phosphate binders in those patients with hyperphosphatemia as frequently seen in renal osteodystrophy is essential to prevent metastatic calcification ^Label.

Mineral oil interferes with the absorption of lipid-soluble vitamins, including vitamin d preparations ^Label.

The administration of thiazide diuretics to hypoparathyroid patients who are concurrently being treated with vitamin d can result in hypercalcemia ^Label.

At this time, no long term animal studies have been performed to evaluate vitamin potential for carcinogens, mutagenesis, or fertility ^Label.

As various animal reproduction studies have demonstrated fetal abnormalities in several species associated with hypervitaminosis D, the use of vitamin d in excess of the recommended dietary allowance during normal pregnancy should be avoided ^Label. The safety in excess of 400 USP units of vitamin d daily during pregnancy has not been established ^Label. The abnormalities observed are similar to the supravalvular aortic stenosis syndrome described in infants that is characterized by supravalvular aortic stenosis, elfin facies, and mental retardation ^Label.

In a nursing mother given large doses of vitamin D, 25-hydroxycholecalciferol appeared in the milk and caused hypercalcemia in her child. Caution is subsequently required when contemplating the use of vitamin d in a nursing woman, and the necessity of monitoring infants' serum calcium concentration if vitamin d is administered to a breastfeeding woman ^Label.

Adverse reactions associated with the use of vitamin d are primarily linked to having hypervitaminosis D occurring [FDA Lanel]. In particular, hypervitaminosis D is characterized by effects specific effects on specific organ systems. At the renal system, hypervitaminosis D can cause impairment of renal function with polyuria, nocturne, polydipsia, hypercalciuria, reversible asotemia, hypertension, nephrocalcinosis, generalized vascular calcification, or even irreversible renal insufficiency which may result in death ^Label. Elsewhere, hypervitaminosis D can also cause CNS mental retardation ^Label. At the level of soft tissues, it can widespread calcification of the soft tissues, including the heart, blood vessels, renal tubules, and lungs ^Label. In the skeletal system, bone demineralization (osteoporosis) in adults can occur while a decline in the average rate of linear growth and increased mineralization of bones, dwarfism, vague aches, stiffness, and weakness can occur in infants and children ^Label. Finally, hypervitaminosis D can also lead to nausea, anorexia, and constipation at the gastrointestinal level as well as mild acidosis, anemia, or weight loss via metabolic processes ^Label.

The LD(50) in animals is unknown ^Label.

Pathways

Not Available

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Not Available

Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abametapir	The serum concentration of Vitamin D can be increased when it is combined with Abametapir.
Acetyldigitoxin	The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Vitamin D is combined with Acetyldigitoxin.
Alfacalcidol	The risk or severity of adverse effects can be increased when Alfacalcidol is combined with Vitamin D.
Aluminum hydroxide	The serum concentration of Aluminum hydroxide can be increased when it is combined with Vitamin D.
Amiodarone	The metabolism of Vitamin D can be decreased when combined with Amiodarone.

Food Interactions

• Take with or without food. Recommendations vary from product to product - consult individual product monographs for additional information.

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Active Moieties

Name	Kind	UNII	CAS	InChI Key
Cholecalciferol	unknown	1C6V77QF41	67-97-0	QYSXJUFSXHHAJI-YRZJJWOYSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Ostoforte	Capsule	50000 unit	Oral	Merck Ltd.	1951-12-31	2007-10-31
Radiostol Solution 100000iu/ml	Liquid	100000 unit / mL	Oral	Allen & Hanburys A Glaxo Canada Ltd. Co.	1951-12-31	1996-09-10

Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Theraplex D Tab 250unit	Tablet	250 unit / tab	Oral	Therapeutic Foods Co.	1987-12-31	1996-09-09
Vitamin D	Tablet	400 unit / tab	Oral	Health Wise Nutrition Inc.	2000-04-03	2002-07-18
Vitamin D 1000 Iu Tablets	Tablet	1000 unit	Oral	Natural Factors Nutritional Products Ltd.	1988-12-31	2008-07-17
Vitamin D 200unit	Capsule	200 unit / cap	Oral	Swiss Herbal Remedies Ltd.	1972-12-31	1999-08-13
Vitamin D Tab 1000unit	Tablet	1000 unit	Oral	Swiss Herbal Remedies Ltd.	1974-12-31	2009-08-04

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
50 Plus	Vitamin D (400 unit) + Ascorbic acid (200 mg) + Biotin (20 mcg) + Choline bitartrate (20 mg) + Cyanocobalamin (20 mcg) + Folic acid (.2 mg) + Inositol (20 mg) + Niacin (20 mg) + Calcium pantothenate (20 mg) + Pyridoxine hydrochloride (20 mg) + Racemethionine (20 mg) + Riboflavin (20 mg) + Thiamine hydrochloride (20 mg) + Vitamin A palmitate (10000 unit) + Vitamin E (20 unit)	Tablet	Oral	Quest Vitamins A Div Of Purity Life Health Products	1998-08-04	2001-07-06
A and D Ointment	Vitamin D (213 unit / g) + Vitamin A (1500 unit / g)	Ointment	Topical	Schering Plough	1951-12-31	2002-07-12
A D Calcium Tab	Vitamin D (400 unit) + Calcium (126 mg) + Vitamin A (5000 unit)	Tablet	Oral	Star Pharmaceuticals, Llc	1979-12-31	1999-07-21
A-D Calcium Cap	Vitamin D (133 unit) + Calcium (170 mg) + Vitamin A (2500 unit)	Capsule	Oral	Vitalab	1990-12-31	2005-07-12
Ad & Calcium Cap	Vitamin D (133 unit) + Calcium (170 mg) + Vitamin A (2500 unit)	Capsule	Oral	Laboratoire Lalco Inc.	1977-12-31	2001-10-15

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
CitraNatal 90 DHA	Vitamin D (400 [iU]/1) + Ascorbic acid (120 mg/1) + Calcium citrate tetrahydrate (159 mg/1) + Cupric oxide (2 mg/1) + Docusate sodium (50 mg/1) + Ferrous gluconate dihydrate (5 mg/1) + Folic acid (1 mg/1) + Iron (85 mg/1) + Nicotinamide (20 mg/1) + Potassium Iodide (150 ug/1) + Pyridoxine hydrochloride (20 mg/1) + Riboflavin (3.4 mg/1) + Thiamine chloride (3 mg/1) + Thiamine mononitrate (4.54 mg/1) + Zinc oxide (25 mg/1) + alpha-Tocopherol acetate (30 [iU]/1)	Tablet	Oral	Mission Pharmacal Company	2014-04-11	Not applicable
CitraNatal 90 DHA	Vitamin D (400 [iU]/1) + Ascorbic acid (120 mg/1) + Calcium citrate tetrahydrate (160 mg/1) + Cupric oxide (2 mg/1) + Docusate sodium (50 mg/1) + Folic acid (1 mg/1) + Iron (90 mg/1) + Nicotinamide (20 mg/1) + Potassium triiodide (150 ug/1) + Pyridoxine hydrochloride (20 mg/1) + Riboprine (3.4 mg/1) + Thiamine chloride (3 mg/1) + Zinc oxide (25 mg/1) + alpha-Tocopherol acetate (30 [iU]/1)	Tablet	Oral	Mission Pharmacal	2010-02-01	Not applicable
CitraNatal DHA	Vitamin D (400 [iU]/1) + Ascorbic acid (120 mg/1) + Calcium citrate tetrahydrate (125 mg/1) + Cupric oxide (2 mg/1) + Docusate sodium (50 mg/1) + Folic acid (1 mg/1) + Iron (27 mg/1) + Nicotinamide (20 mg/1) + Potassium Iodide (150 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Riboflavin (3.4 mg/1) + Thiamine chloride (3 mg/1) + Zinc oxide (25 mg/1) + alpha-Tocopherol acetate (30 [iU]/1)	Tablet	Oral	Mission Pharmacal	2007-11-20	Not applicable
CitraNatal DHA	Vitamin D (400 [iU]/1) + Ascorbic acid (120 mg/1) + Calcium citrate tetrahydrate (124 mg/1) + Cupric oxide (2 mg/1) + Doconexent (250 mg/1) + Docusate sodium (50 mg/1) + Folic acid (1 mg/1) + Icosapent (0.625 mg/1) + Iron (27 mg/1) + Nicotinamide (20 mg/1) + Potassium Iodide (150 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Riboflavin (3.4 mg/1) + Thiamine chloride (3 mg/1) + Zinc oxide (25 mg/1) + alpha-Tocopherol acetate (30 [iU]/1)	Kit	Oral	Mission Pharmacal Company	2014-05-22	Not applicable
CitraNatal Rx	Vitamin D (400 [iU]/1) + Ascorbic acid (120 mg/1) + Calcium citrate tetrahydrate (124 mg/1) + Cupric oxide (2 mg/1) + Folic acid (1 mg/1) + Iron (27 mg/1) + Nicotinamide (20 mg/1) + Potassium Iodide (150 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Riboflavin (3.4 mg/1) + Thiamine chloride (3 mg/1) + Zinc oxide (25 mg/1) + alpha-Tocopherol acetate (30 [iU]/1)	Tablet	Oral	Mission Pharmacal	2014-08-11	Not applicable

Categories

Drug Categories

• Bone Density Conservation Agents
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 CYP3A4 Substrates (strength unknown)
• Cytochrome P-450 Substrates
• Diet, Food, and Nutrition
• Food
• Fused-Ring Compounds
• Micronutrients
• Physiological Phenomena
• Secosteroids
• Steroids
• Vitamin D and Analogues
• Vitamins
• Vitamins (Fat Soluble)

Classification

Not classified

Affected organisms

Not Available

Chemical Identifiers

UNII

9VU1KI44GP

CAS number

1406-16-2

References

General References

1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [Article]
2. DeLuca HF: Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1689S-96S. [Article]
3. DeLuca HF: Metabolism of vitamin D: current status. Am J Clin Nutr. 1976 Nov;29(11):1258-70. [Article]
4. Jones KS, Assar S, Harnpanich D, Bouillon R, Lambrechts D, Prentice A, Schoenmakers I: 25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype. J Clin Endocrinol Metab. 2014 Sep;99(9):3373-81. doi: 10.1210/jc.2014-1714. Epub 2014 Jun 2. [Article]
5. 2. (1984). In Vitamin D: Basic and Clinical Aspects (pp. 81). Martinus Nijhoff Publishing. [ISBN:978-1-4612-9793-2]
6. Vitamin D Supplementation: An Update [Link]
7. Sandoz: PediaVit D (vitamin D) oral solution [Link]

External Links

PubChem Substance

347911113

RxNav

11253

Wikipedia

Vitamin_D

FDA label

Download (175 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Prevention	Food Allergy	1
4	Active Not Recruiting	Treatment	Coronavirus Disease 2019 (COVID‑19) / COVID-19 Respiratory Infection	1
4	Completed	Not Available	Osteopenia (Disorder)	1
4	Completed	Basic Science	Deficiency, Vitamin D	2
4	Completed	Diagnostic	Polycystic Ovarian Syndrome (PCOS)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Ointment	Topical
Syrup	Oral
Tablet, film coated	Oral
Cream	Topical
Wafer	Oral
Tablet	Oral
Liquid	Oral
Tablet, extended release	Oral
Solution	Oral	100000 IU
Tablet, film coated
Lozenge	Oral
Tablet, coated	Oral	150 mcg
Capsule	Oral	0.266 mg
Liquid	Intravenous
Solution	Intravenous
Elixir	Oral
Liquid; tablet	Oral
Tablet, chewable	Oral
Tablet, sugar coated	Oral
Kit	Oral
Capsule	Oral	50000 unit
Capsule, coated	Oral
Liquid	Oral	100000 unit / mL
Capsule, gelatin coated	Oral
Tablet, effervescent	Oral
Emulsion	Oral
Tablet, coated	Oral
Tablet	Oral	250 unit / tab
Capsule; liquid	Oral
Solution / drops	Oral
Solution	Oral
Capsule	Oral
Capsule, liquid filled; kit	Oral
Capsule, liquid filled	Oral
Capsule; kit; tablet, coated	Oral
Tablet	Oral	400 unit / tab
Capsule	Oral	200 unit / cap
Tablet	Oral	1000 unit
Capsule	Oral	195 unit / cap
Powder	Oral

Prices

Not Available

Patents

Not Available

Properties

State

Not Available

Experimental Properties

Not Available

Predicted Properties

Not Available

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

Chromatographic Properties

Collision Cross Sections (CCS)

Not Available

Targets

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Details1. Vitamin D3 receptor

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

General Function

Zinc ion binding

Specific Function

Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Recruited to promoters via its interaction with BAZ1B...

Gene Name

VDR

Uniprot ID

P11473

Uniprot Name

Vitamin D3 receptor

Molecular Weight

48288.64 Da

References

1. Choi M, Yamada S, Makishima M: Dynamic and ligand-selective interactions of vitamin D receptor with retinoid X receptor and cofactors in living cells. Mol Pharmacol. 2011 Dec;80(6):1147-55. doi: 10.1124/mol.111.074138. Epub 2011 Sep 14. [Article]

Details2. Vitamin D-binding protein

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

General Function

Vitamin transporter activity

Specific Function

Involved in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5 alpha for neutrophils in inflammation and macrophage activation.

Gene Name

GC

Uniprot ID

P02774

Uniprot Name

Vitamin D-binding protein

Molecular Weight

52963.025 Da

References

1. Arnaud J, Constans J: Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet. 1993 Sep;92(2):183-8. [Article]

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Drug created at December 03, 2015 16:51 / Updated at February 20, 2024 23:55