Peringatan Keamanan

LD50 (oral, rat) = 620 μg/kg; LD50 (intraperitoneal, rat) > 5 mg/kg MSDS.

Symptoms of calcitriol toxicity mirrors the early and late signs and symptoms of vitamin D intoxication associated with hypercalcemia L5653. Early signs include weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain and metallic taste. Late signs are characterized by polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated SGOT and SGPT, ectopic calcification, hypertension, cardiac arrhythmias and, rarely, overt psychosis L5653.

Calcitriol

DB00136

small molecule approved nutraceutical

Deskripsi

Calcitriol is an active metabolite of vitamin D with 3 hydroxyl (OH) groups and is commonly referred to as 1,25-dihydroxycholecalciferol, or 1alpha,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D3. It is produced in the body after series of conversion steps of 7-dehydrocholesterol from exposure to UV light. 7-dehydrocholesterol is converted to DB00169 (vitamin D3) in the skin, which is then converted to DB00146 in the liver and kidneys. DB00146 undergoes hydroxylation to form calcitriol via 1?-hydroxylase (CYP27B1) activity A26353. Calcitriol is considered to be the most potent metabolite of vitamin D in humans A3366. Renal production of calcitriol is stimulated in response to PTH, low calcium and low phosphate A26353. Calcitriol plays a role in plasma calcium regulation in concert with parathyroid hormone (PTH) by enhancing absorption of dietary calcium and phosphate from the gastrointestinal tract, promoting renal tubular reabsorption of calcium in the kidneys, and stimulating the release of calcium stores from the skeletal system. In addition to promoting fatty acid synthesis and inhibiting lipolysis, calcitriol has been demonstrated to increase energy efficiency by suppressing UCP2 expression, which is modulated by signaling pathways of classical nuclear receptors (nVDR), where calcitriol acts as a natural ligand A175615. There is also evidence that calcitriol modulates the action of cytokines and may regulate immune and inflammatory response, cell turnover, cell differentiation A26353.

Administered orally and intravenously, calcitriol is commonly used as a medication in the treatment of secondary hyperparathyroidism and resultant metabolic bone disease, hypocalcemia in patients undergoing chronic renal dialysis, and osteoporosis. It is also available in topical form for the treatment of mild to moderate plaque psoriasis in adults. Calcitriol is marketed under various trade names including Rocaltrol (Roche), Calcijex (Abbott) and Decostriol (Mibe, Jesalis).

Struktur Molekul 2D

Berat 416.6365
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) After administration of single oral doses, the elimination half life was 5-8 hours [FDA Label].
Volume Distribusi Upon intravenous administration, the volume of distribution of calcitriol was 0.49±0.14 L/kg in healthy male volunteers and 0.27±0.06?l/kg in uraemic male patients participating in a pharmacokinetic study [A175726]. There is some evidence that calcitriol is transferred into human milk at low levels (ie, 2.2±0.1 pg/mL) in mothers [FDA Label]. Calcitriol from maternal circulation may also enter the fetal circulation [FDA Label].
Klirens (Clearance) The metabolic clearance rate was 23.5±4.34 ml/min in healthy male volunteers and 10.1±1.35 ml/min in male patients with uraemia [A175726]. In the pediatric patients undergoing peritoneal dialysis receiving dose of 10.2 ng/kg (SD 5.5 ng/kg) for 2 months, the clearance rate was 15.3 mL/hr/kg [FDA Label].

Absorpsi

Upon administration, calcitriol is rapidly absorbed from the intestines. When a single oral dose of 0.5 mcg of calcitriol was administered, the mean serum concentrations of calcitriol rose from a baseline value of 40.0±4.4 (SD) pg/mL to 60.0±4.4 pg/mL at 2 hours, and declined to 53.0±6.9 at 4 hours, 50±7.0 at 8 hours, 44±4.6 at 12 hours and 41.5±5.1 at 24 hours FDA Label. Following administration of single doses of 0.25 to 1.0 mcg of calcitriol, the peak plasma concentrations were reached within 3 to 6 hours FDA Label. In a pharmacokinetic study, the oral bioavailability was 70.6±5.8% in healthy male volunteers and 72.2±4.8% in male patients with uraemia A175726.

Metabolisme

Metabolism of calcitriol involves two pathways FDA Label. The first pathway involves 24-hydroxylase activity in the kidney; this enzyme is also present in many target tissues which possess the vitamin D receptor such as the intestine. The end product of this pathway is a side chain shortened metabolite, calcitroic acid. The second pathway involves the conversion of calcitriol via the stepwise hydroxylation of carbon-26 and carbon-23, and cyclization to yield ultimately 1a,25R(OH)2-26,23S-lactone D3, which appears to be the major metabolite circulating in humans. Ohter identified metabolites of calcitriol include 1?, 25(OH)2-24-oxo-D3; 1?, 23,25(OH)3-24-oxo-D3; 1?, 24R,25(OH)3D3; 1?, 25S,26(OH)3D3; 1?, 25(OH)2-23-oxo-D3; 1?, 25R,26(OH)3-23-oxo-D3 and 1?, (OH)24,25,26,27-tetranor-COOH-D3 FDA Label.

Rute Eliminasi

In normal subjects, approximately 27% and 7% of the radioactivity appeared in the feces and urine, respectively, within 24 hours FDA Label. Calcitriol undergoes enterohepatic recycling and biliary excretion. The metabolites of calcitriol are excreted primarily in feces. Cumulative excretion of radioactivity on the sixth day following intravenous administration of radiolabeled calcitriol averaged 16% in urine and 49% in feces FDA Label.

Interaksi Obat

451 Data
Aluminum hydroxide The serum concentration of Aluminum hydroxide can be increased when it is combined with Calcitriol.
Aripiprazole The metabolism of Aripiprazole can be increased when combined with Calcitriol.
Aripiprazole lauroxil The metabolism of Aripiprazole lauroxil can be increased when combined with Calcitriol.
Danazol Danazol may increase the hypercalcemic activities of Calcitriol.
Sucralfate The serum concentration of Sucralfate can be increased when it is combined with Calcitriol.
Orlistat Orlistat can cause a decrease in the absorption of Calcitriol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ifosfamide The metabolism of Ifosfamide can be increased when combined with Calcitriol.
Perampanel The metabolism of Perampanel can be increased when combined with Calcitriol.
Magnesium sulfate The serum concentration of Magnesium sulfate can be increased when it is combined with Calcitriol.
Magnesium oxide The serum concentration of Magnesium oxide can be increased when it is combined with Calcitriol.
Magnesium salicylate The serum concentration of Magnesium salicylate can be increased when it is combined with Calcitriol.
Magaldrate The serum concentration of Magaldrate can be increased when it is combined with Calcitriol.
Magnesium hydroxide The serum concentration of Magnesium hydroxide can be increased when it is combined with Calcitriol.
Magnesium trisilicate The serum concentration of Magnesium trisilicate can be increased when it is combined with Calcitriol.
Magnesium chloride The serum concentration of Magnesium chloride can be increased when it is combined with Calcitriol.
Magnesium carbonate The serum concentration of Magnesium carbonate can be increased when it is combined with Calcitriol.
Talc The serum concentration of Talc can be increased when it is combined with Calcitriol.
Magnesium citrate The serum concentration of Magnesium citrate can be increased when it is combined with Calcitriol.
Magnesium silicate The serum concentration of Magnesium silicate can be increased when it is combined with Calcitriol.
Hydrotalcite The serum concentration of Hydrotalcite can be increased when it is combined with Calcitriol.
Magnesium aspartate The serum concentration of Magnesium aspartate can be increased when it is combined with Calcitriol.
Magnesium peroxide The serum concentration of Magnesium peroxide can be increased when it is combined with Calcitriol.
Magnesium gluconate The serum concentration of Magnesium gluconate can be increased when it is combined with Calcitriol.
Magnesium orotate The serum concentration of Magnesium orotate can be increased when it is combined with Calcitriol.
Magnesium The serum concentration of Magnesium can be increased when it is combined with Calcitriol.
Magnesium levulinate The serum concentration of Magnesium levulinate can be increased when it is combined with Calcitriol.
Magnesium lactate The serum concentration of Magnesium lactate can be increased when it is combined with Calcitriol.
Warfarin The metabolism of Warfarin can be increased when combined with Calcitriol.
Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Calcitriol.
(R)-warfarin The metabolism of (R)-warfarin can be increased when combined with Calcitriol.
R,S-Warfarin alcohol The metabolism of R,S-Warfarin alcohol can be increased when combined with Calcitriol.
S,R-Warfarin alcohol The metabolism of S,R-Warfarin alcohol can be increased when combined with Calcitriol.
(S)-Warfarin The metabolism of (S)-Warfarin can be increased when combined with Calcitriol.
Digoxin The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Digoxin.
Acetyldigitoxin The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Acetyldigitoxin.
Deslanoside The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Deslanoside.
Ouabain The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Ouabain.
Oleandrin The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Oleandrin.
Cymarin The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Cymarin.
Proscillaridin The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Proscillaridin.
Metildigoxin The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Metildigoxin.
Lanatoside C The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Lanatoside C.
Gitoformate The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Gitoformate.
Acetyldigoxin The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Acetyldigoxin.
Peruvoside The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Calcitriol is combined with Peruvoside.
Mineral oil Mineral oil can cause a decrease in the absorption of Calcitriol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Methyclothiazide The risk or severity of hypercalcemia can be increased when Methyclothiazide is combined with Calcitriol.
Bendroflumethiazide The risk or severity of hypercalcemia can be increased when Bendroflumethiazide is combined with Calcitriol.
Benzthiazide The risk or severity of hypercalcemia can be increased when Benzthiazide is combined with Calcitriol.
Cyclothiazide The risk or severity of hypercalcemia can be increased when Cyclothiazide is combined with Calcitriol.
Hydroflumethiazide The risk or severity of hypercalcemia can be increased when Hydroflumethiazide is combined with Calcitriol.
Chlorothiazide The risk or severity of hypercalcemia can be increased when Chlorothiazide is combined with Calcitriol.
Hydrochlorothiazide The risk or severity of hypercalcemia can be increased when Hydrochlorothiazide is combined with Calcitriol.
Trichlormethiazide The risk or severity of hypercalcemia can be increased when Trichlormethiazide is combined with Calcitriol.
Polythiazide The risk or severity of hypercalcemia can be increased when Polythiazide is combined with Calcitriol.
Mebutizide The risk or severity of hypercalcemia can be increased when Mebutizide is combined with Calcitriol.
Cyclopenthiazide The risk or severity of hypercalcemia can be increased when Cyclopenthiazide is combined with Calcitriol.
Buthiazide The risk or severity of hypercalcemia can be increased when Buthiazide is combined with Calcitriol.
Calcifediol The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcifediol.
Ergocalciferol The risk or severity of adverse effects can be increased when Calcitriol is combined with Ergocalciferol.
Cholecalciferol The risk or severity of adverse effects can be increased when Calcitriol is combined with Cholecalciferol.
Paricalcitol The risk or severity of adverse effects can be increased when Calcitriol is combined with Paricalcitol.
Dihydrotachysterol The risk or severity of adverse effects can be increased when Calcitriol is combined with Dihydrotachysterol.
Alfacalcidol The risk or severity of adverse effects can be increased when Calcitriol is combined with Alfacalcidol.
Seocalcitol The risk or severity of adverse effects can be increased when Calcitriol is combined with Seocalcitol.
Inecalcitol The risk or severity of adverse effects can be increased when Calcitriol is combined with Inecalcitol.
Becocalcidiol The risk or severity of adverse effects can be increased when Calcitriol is combined with Becocalcidiol.
Eldecalcitol The risk or severity of adverse effects can be increased when Calcitriol is combined with Eldecalcitol.
1alpha,24S-Dihydroxyvitamin D2 The risk or severity of adverse effects can be increased when Calcitriol is combined with 1alpha,24S-Dihydroxyvitamin D2.
Elocalcitol The risk or severity of adverse effects can be increased when Calcitriol is combined with Elocalcitol.
Maxacalcitol The risk or severity of adverse effects can be increased when Calcitriol is combined with Maxacalcitol.
Doxercalciferol The risk or severity of adverse effects can be increased when Calcitriol is combined with Doxercalciferol.
Vitamin D The risk or severity of adverse effects can be increased when Calcitriol is combined with Vitamin D.
1alpha-Hydroxyvitamin D5 The risk or severity of adverse effects can be increased when Calcitriol is combined with 1alpha-Hydroxyvitamin D5.
Previtamin D(3) The risk or severity of adverse effects can be increased when Calcitriol is combined with Previtamin D(3).
Calcium acetate The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium acetate.
Calcium glucoheptonate The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium glucoheptonate.
Calcium chloride The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium chloride.
Calcium The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium.
Calcium carbonate The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium carbonate.
Calcium citrate The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium citrate.
Calcium gluconate The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium gluconate.
Calcium Phosphate The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium Phosphate.
Calcium glubionate anhydrous The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium glubionate anhydrous.
Calcium lactate The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium lactate.
Calcium lactate gluconate The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium lactate gluconate.
Calcium pangamate The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium pangamate.
Calcium levulinate The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium levulinate.
Calcium cation The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium cation.
Calcium polycarbophil The risk or severity of adverse effects can be increased when Calcitriol is combined with Calcium polycarbophil.
Colestipol The serum concentration of Calcitriol can be decreased when it is combined with Colestipol.
Colesevelam The serum concentration of Calcitriol can be decreased when it is combined with Colesevelam.
Cholestyramine The serum concentration of Calcitriol can be decreased when it is combined with Cholestyramine.
Tixocortol The therapeutic efficacy of Calcitriol can be decreased when used in combination with Tixocortol.
Fluocortin The therapeutic efficacy of Calcitriol can be decreased when used in combination with Fluocortin.
Fluperolone The therapeutic efficacy of Calcitriol can be decreased when used in combination with Fluperolone.
Fluclorolone The therapeutic efficacy of Calcitriol can be decreased when used in combination with Fluclorolone.
Budesonide The therapeutic efficacy of Calcitriol can be decreased when used in combination with Budesonide.
Flunisolide The therapeutic efficacy of Calcitriol can be decreased when used in combination with Flunisolide.
Beclomethasone dipropionate The therapeutic efficacy of Calcitriol can be decreased when used in combination with Beclomethasone dipropionate.

Target Protein

Vitamin D3 receptor VDR
Homeobox protein Hox-A10 HOXA10

Referensi & Sumber

Synthesis reference: Raymond E. Conrow, "Process for preparation of calcitriol lactone and related intermediates." U.S. Patent US5457245, issued April, 1994.
Artikel (PubMed)
  • PMID: 17396166
    Brawer MK: Recent Progress in the Treatment of Advanced Prostate Cancer With Intermittent Dose-Intense Calcitriol (DN-101). Rev Urol. 2007 Winter;9(1):1-8.
  • PMID: 16278401
    Beer TM, Javle M, Lam GN, Henner WD, Wong A, Trump DL: Pharmacokinetics and tolerability of a single dose of DN-101, a new formulation of calcitriol, in patients with cancer. Clin Cancer Res. 2005 Nov 1;11(21):7794-9.
  • PMID: 18844841
    Zemel MB, Sun X: Calcitriol and energy metabolism. Nutr Rev. 2008 Oct;66(10 Suppl 2):S139-46. doi: 10.1111/j.1753-4887.2008.00099.x.
  • PMID: 23713873
    Rodriguez M, Munoz-Castaneda JR, Almaden Y: Therapeutic use of calcitriol. Curr Vasc Pharmacol. 2014 Mar;12(2):294-9.
  • PMID: 7827399
    Dechant KL, Goa KL: Calcitriol. A review of its use in the treatment of postmenopausal osteoporosis and its potential in corticosteroid-induced osteoporosis. Drugs Aging. 1994 Oct;5(4):300-17. doi: 10.2165/00002512-199405040-00006.
  • PMID: 28429545
    Toussaint ND, Damasiewicz MJ: Do the benefits of using calcitriol and other vitamin D receptor activators in patients with chronic kidney disease outweigh the harms? Nephrology (Carlton). 2017 Mar;22 Suppl 2:51-56. doi: 10.1111/nep.13026.
  • PMID: 12528991
    Farach-Carson MC, Nemere I: Membrane receptors for vitamin D steroid hormones: potential new drug targets. Curr Drug Targets. 2003 Jan;4(1):67-76.
  • PMID: -
    Brandi L, Egfjord M, Olgaard K: Pharmacokinetics of 1,25(OH)2D3 and 1α(OH)D3 in normal and uraemic men Nephrology Dialysis Transplantation. 2002 May 1;17(5):829–842.
Menampilkan 8 dari 9 artikel.

Contoh Produk & Brand

Produk: 109 • International brands: 3
Produk
  • Calcijex
    Injection, solution • 1 ug/1mL • Intravenous • US • Approved
  • Calcijex
    Solution • 1 mcg / mL • Intravenous • Canada • Approved
  • Calcijex
    Solution • 2 mcg / mL • Intravenous • Canada • Approved
  • Calcitriol
    Solution • 1 ug/1mL • Intravenous • US • Approved
  • Calcitriol
    Capsule, liquid filled • 0.25 ug/1 • Oral • US • Generic • Approved
  • Calcitriol
    Capsule, liquid filled • 0.5 ug/1 • Oral • US • Generic • Approved
  • Calcitriol
    Injection • 1 ug/1mL • Intravenous • US • Generic • Approved
  • Calcitriol
    Injection, solution • 1 mg/1mL • Intravenous • US • Generic • Approved
Menampilkan 8 dari 109 produk.
International Brands
  • Asentar — Novacea
  • Calcitriol Oral Solution — Roxane
  • Decostriol — Mibe Jena (Germany), Jesalis (Hong Kong, Thailand)

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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