Dihydrotachysterol stimulates intestinal calcium absorption and mobilizes bone calcium to successfully raise serum calcium levels in the absence of parathyroid hormone and functional renal tissue [1]. Renal phosphate excretion can also be elevated by dihydrotachysterol [1].

A popular and powerful synthetic analog of vitamin D that costs more than vitamin D2 is dihydrotachysterol. Its half-life and onset time fall between that of calcitriol and vitamin D2. Hypoparathyroidism may be treated with dihydrotachysterol (final dose range: 0.004 to 0.04 mg/kg/day; first dose: 0.03 to 0.08 mg/kg/day for 2 to 3 days) [2].

Animal/Disease Models: Animal/Disease Models: 5 mixed-housed young to middle-aged cats [2]
Doses: Initial dose is 0.03 to 0.08 mg/kg/day for 2 to 3 days. The final dose range is 0.004 to 0.04 mg/kg/day.
Route of Administration: Oral
Experimental Results: Effective in the treatment of hypoparathyroidism.

Absorption, Distribution and Excretion
Onset of Action: Hypercalcemia: Several hours (peak after 1 to 2 weeks). The primary elimination pathway for dihydrotachysterol and its metabolites is likely secretion into bile and excretion in feces. Dihydrotachysterol is also secreted into breast milk. Duration of Action: After oral administration: Up to 9 weeks. The primary excretion route for vitamin D is bile; only a small amount of the administered dose is excreted in the urine. Vitamin D For more complete data on the absorption, distribution, and excretion of dihydrotachysterol (8 metabolites), please visit the HSDB record page. Metabolism/Metabolites DHT3 (vitamin D3) is hydroxylated at position 25 to form 25-hydroxydihydrotachysterol 3 (25-OHDHT3), which appears to be the active form of DHT (dihydrotachysterol) in the intestine and bone.
Highly radioactive (14)C and (3)H labeled dihydrotachysterols were prepared, and their metabolites were investigated in rickets-ridden chicks and rats. 20% of the dihydrotachysterols were excreted via bile within the first 24 hours, with approximately 50% existing as carboxylic acid derivatives. No C-1 hydroxylation was observed, but polar metabolites were detected in all tissues. A higher proportion of the parent steroid compound and its 25-OH derivatives were detected in tissues compared to cholecalciferol, but no single metabolite was detected at the intracellular site of action of cholecalciferol.

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Biological Half-Life
Absorbed vitamin D circulates in the blood after binding to vitamin D-binding protein (a specific α-globulin). The half-life of vitamin D disappearing from plasma is 19 to 25 hours, but it is stored in the body for extended periods (up to 6 months or longer in rats), apparently as a form of fatty deposits throughout the body. /Vitamin D/

Toxicity Summary
This drug, after hydroxylation to 25-hydroxydihydrotachysterol, binds to vitamin D receptors. The bound vitamin D receptor acts as a transcriptional regulator of bone matrix proteins, inducing osteocalcin expression and inhibiting type I collagen synthesis. Vitamin D (after binding to its receptor) stimulates the expression of various proteins involved in calcium transport, responsible for transporting calcium from the intestinal lumen across epithelial cells into the bloodstream. This stimulates intestinal calcium absorption and increases renal phosphate excretion. These functions are normally performed by parathyroid hormone. Protein Binding 99% Interactions Corticosteroids antagonize the effects of vitamin D analogs. /Vitamin D Analogs/ In patients with hypoparathyroidism, concomitant use of thiazide diuretics and pharmacological doses of vitamin D analogs may lead to hypercalcemia, which may be transient and self-limiting, or may require discontinuation of the vitamin D analog. Hypercalcemia induced by thiazide diuretics in patients with hypoparathyroidism may be due to increased calcium release from bones. /Vitamin D analogs/
Excessive use of mineral oil may interfere with intestinal absorption of vitamin D analogs. /Vitamin D analogs/
Orlistat may reduce the gastrointestinal absorption of fat-soluble vitamins (such as vitamin D analogs). At least 2 hours should be allowed between taking any dose of orlistat and taking a vitamin D analog (before or after). /Vitamin D analogs/
For more complete data on interactions of dihydroisothiophenols (6 in total), please visit the HSDB records page.

[1]. Dihydrotachysterol therapy for hypoparathyroidism: consequences of inadequate monitoring. Five cases and a review. Exp Clin Endocrinol Diabetes. 2005 Jul;113(7):376-80.

[2]. Idiopathic hypoparathyroidism in five cats. J Vet Intern Med. Jan-Feb 1991;5(1):47-51.

Dihydrotachysterol is a hydroxyl-opening ring-sterol compound with the structure 9,10-open-ergoster-5,7,22-triene, substituted with a hydroxyl group at the 3-position. It is a synthetic analog of vitamin D and has bone density-protective effects. It is a vitamin D, hydroxyl-opening ring-sterol, and open-ring ergosterane compound. Dihydrotachysterol can be considered a reduction product of vitamin D2. Dihydrotachysterol is only present in individuals who have taken this drug. It is a vitamin D and can be considered a reduction product of vitamin D2. [PubChem] After hydroxylation to 25-hydroxydihydrotachysterol, this modified drug binds to the vitamin D receptor. The bound vitamin D receptor acts as a transcriptional regulator of bone matrix proteins, inducing osteocalcin expression and inhibiting type I collagen synthesis. Vitamin D (after binding to the vitamin D receptor) stimulates the expression of various proteins involved in calcium transport, which transport calcium from the intestinal lumen across epithelial cells into the bloodstream. This promotes intestinal calcium absorption and increases renal phosphate excretion. These functions are typically performed by parathyroid hormone. Vitamin D can be considered a reduction product of vitamin D2. Drug Indications: Used for the prevention and treatment of rickets or osteomalacia, and for the treatment of hypocalcemia associated with hypoparathyroidism or pseudohypoparathyroidism. Also used to treat vitamin D-dependent rickets, rickets or osteomalacia caused by long-term high-dose anticonvulsant therapy, early renal osteodystrophy, osteoporosis (requires combination with calcium supplements), and hypophosphatemia associated with Fanconi syndrome (requires treatment of acidosis). Mechanism of Action: After hydroxylation to 25-hydroxydihydrotachysterol, this drug binds to vitamin D receptors. The bound vitamin D receptors act as transcriptional regulators of bone matrix proteins, inducing osteocalcin expression and inhibiting type I collagen synthesis. Vitamin D (after binding to vitamin D receptors) stimulates the expression of various proteins involved in calcium transport, which transport calcium from the intestinal lumen across epithelial cells into the bloodstream. This promotes intestinal calcium absorption and increases renal phosphate excretion. These functions are normally performed by parathyroid hormone. Serum calcium concentrations are increased by increasing intestinal calcium absorption and possibly by enhancing urinary excretion of inorganic phosphates… Drug-induced phosphateuria may be due to elevated serum calcium levels and their effect on renal phosphate clearance.

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Therapeutic Uses
Bone mineral density protectant; Vitamin
Veterinary Drug: Calcium regulator used in veterinary medicine to treat hypercalcemia.
Dihydrotachysterol is indicated for the treatment of chronic and latent postoperative tetany and idiopathic tetany. /US Product Labels Include/
Therapeutic doses of certain vitamin D analogs are used to treat chronic hypocalcemia, hypophosphatemia, rickets, and osteodystrophy associated with a variety of conditions, including chronic renal failure, familial hypophosphatemia, and hypoparathyroidism (postoperative, idiopathic, or pseudohypoparathyroidism). Some analogs have been found to reduce elevated parathyroid hormone levels in patients with renal osteodystrophy accompanied by hyperparathyroidism. Theoretically, any vitamin D analog can be used to treat the above conditions, but due to their different pharmacological properties, some analogs may be more effective than others in specific situations. For patients with renal failure, alfacalcidol, calcitriol, and dihydrotachysterol are usually preferred because these patients have impaired ability to synthesize calcitriol from cholecalciferol and ergocalciferol; therefore, the treatment response is more predictable. Furthermore, due to their shorter half-life, toxicity is easier to control (hypercalcemia is reversed more quickly). Ergocalciferol may not be the first-line treatment for familial hypophosphatemia or hypoparathyroidism because the high doses required are associated with the risk of overdose and hypercalcemia; dihydrotachysterol and calcitriol may be better options. /US product label contains/

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Drug Warning
/Dihydrotachysterol/…should not be used in cases of renal insufficiency or hyperphosphatemia. Extra caution must be taken to prevent overdose.
Vitamin D analogs are generally non-toxic when the dose does not exceed physiological requirements. However, some infants and patients with sarcoidosis or hypoparathyroidism may be more sensitive to vitamin D analogs. Vitamin D analogs
Acute or chronic overdose of vitamin D analogs, or an enhanced response to physiological doses of ergocalciferol or cholecalciferol, can lead to vitamin D overdose, manifested as hypercalcemia. Vitamin D analogs
Long-term use of vitamin D analogs to treat hypoparathyroidism has been reported to result in decreased renal function without hypercalcemia. Before initiating treatment with vitamin D analogs, serum phosphate levels must be controlled. To avoid ectopic calcification, the ratio of serum calcium (mg/dL) to phosphorus (mg/dL) should not exceed 70. Because taking vitamin D analogs may increase phosphate absorption, patients with renal failure may require dose adjustments of aluminum-containing antacids used to reduce phosphate absorption. Vitamin D Analogs
FDA Pregnancy Risk Classification: Category C/Risk cannot be ruled out. There are currently insufficient and well-controlled human studies, and animal studies have not shown any risk to the fetus. If this drug is taken during pregnancy, it may cause harm to the fetus; however, the potential benefits may outweigh the potential risks. /

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Pharmacodynamics
Dihydrotachysterol is hydroxylated in the liver to 25-hydroxydihydrotachysterol, which is the main circulating active form of the drug. It is not further hydroxylated in the kidneys and is therefore an analog of 1,25-dihydroxyvitamin D. Dihydrotachysterol effectively increases serum calcium levels in the absence of parathyroid hormone and in cases of impaired renal function by stimulating intestinal calcium absorption and mobilizing bone calcium. Dihydrotachysterol can also increase the kidney's excretion of phosphate.

C28H46O

398.66

398.355

C, 84.36; H, 11.63; O, 4.01

67-96-9

67-96-9

5311071

White to off-white solid powder

1.003 g/cm3

499.5ºC at 760 mmHg

131ºC

217.6ºC

1.569

7.72

1

1

5

29

639

7

CC([C@H](/C=C/[C@H]([C@]1(CC[C@]2(/C(=C/C=C3/C[C@@H](O)CC[C@@H]/3C)/CCC[C@]12C)[H])[H])C)C)C

ILYCWAKSDCYMBB-OPCMSESCSA-N

InChI=1S/C28H46O/c1-19(2)20(3)9-10-22(5)26-15-16-27-23(8-7-17-28(26,27)6)12-13-24-18-25(29)14-11-21(24)4/h9-10,12-13,19-22,25-27,29H,7-8,11,14-18H2,1-6H3/b10-9+,23-12+,24-13+/t20-,21-,22+,25-,26+,27-,28+/m0/s1

(1S,3E,4S)-3-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylcyclohexan-1-ol

Dihydrotachysterol; SDB 3314; HSDB3314; HSDB-3314; Parterol; Tachyrol; Hytakerol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)