Tìm theo
Paricalcitol
Các tên gọi khác (3) :
  • 19-Nor-1alpha,25-dihydroxyvitamin D2
  • Paricalcitol
  • Zemplar
Thuốc Gốc
Small Molecule
CAS: 131918-61-1
ATC: H05BX02
ĐG : Abbott Laboratories Ltd. , http://www.abbott.com
CTHH: C27H44O3
PTK: 416.6365
Paricalcitol is a synthetic vitamin D analog. Paricalcitol has been used to reduce parathyroid hormone levels. Paricalcitol is indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C27H44O3
Phân tử khối
416.6365
Monoisotopic mass
416.329045274
InChI
InChI=1S/C27H44O3/c1-18(8-9-19(2)26(3,4)30)24-12-13-25-21(7-6-14-27(24,25)5)11-10-20-15-22(28)17-23(29)16-20/h8-11,18-19,22-25,28-30H,6-7,12-17H2,1-5H3/b9-8+,21-11+/t18-,19+,22-,23-,24-,25+,27-/m1/s1
InChI Key
InChIKey=BPKAHTKRCLCHEA-UBFJEZKGSA-N
IUPAC Name
(1R,3R)-5-{2-[(1R,3aS,4E,7aR)-1-[(2R,3E,5S)-6-hydroxy-5,6-dimethylhept-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}cyclohexane-1,3-diol
Traditional IUPAC Name
paricalcitol
SMILES
[H]C1CC[C@]2(C)[C@]([H])(CC[C@@]2([H])\C1=C\C=C1C[C@@H](O)C[C@H](O)C1)[C@H](C)\C=C\[C@H](C)C(O)(C)C
Độ hòa tan
6.80e-03 g/l
logP
4.5
logS
-4.8
pKa (strongest acidic)
14.81
pKa (Strongest Basic)
-1
PSA
60.69 Å2
Refractivity
127.95 m3·mol-1
Polarizability
51.11 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
3
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Dược Lực Học : Secondary hyperparathyroidism is characterized by an elevation in parathyroid hormone (PTH) associated with inadequate levels of active vitamin D hormone. The source of vitamin D in the body is from synthesis in the skin and from dietary intake. Vitamin D requires two sequential hydroxylations in the liver and the kidney to bind to and to activate the vitamin D receptor (VDR). The endogenous VDR activator, calcitriol [1,25(OH)2 D3], is a hormone that binds to VDRs that are present in the parathyroid gland, intestine, kidney, and bone to maintain parathyroid function and calcium and phosphorus homeostasis, and to VDRs found in many other tissues, including prostate, endothelium and immune cells. VDR activation is essential for the proper formation and maintenance of normal bone. In the diseased kidney, the activation of vitamin D is diminished, resulting in a rise of PTH, subsequently leading to secondary hyperparathyroidism and disturbances in the calcium and phosphorus homeostasis.1 Decreased levels of 1,25(OH)2 D3 have been observed in early stages of chronic kidney disease. The decreased levels of 1,25(OH)2 D3 and resultant elevated PTH levels, both of which often precede abnormalities in serum calcium and phosphorus, affect bone turnover rate and may result in renal osteodystrophy. An in vitro study indicates that paricalcitol is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A at concentrations up to 50 nM (21 ng/mL).
Cơ Chế Tác Dụng : Paricalcitol is a synthetic vitamin D analog. Paricalcitol has been used to reduce parathyroid hormone levels. Paricalcitol is indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure. Paricalcitol is a synthetic, biologically active vitamin D analog of calcitriol with modifications to the side chain (D2) and the A (19-nor) ring. Preclinical andin vitro studies have demonstrated that paricalcitol's biological actions are mediated through binding of the VDR, which results in the selective activation of vitamin D responsive pathways. Vitamin D and paricalcitol have been shown to reduce parathyroid hormone levels by inhibiting PTH synthesis and secretion.
Dược Động Học :
▧ Absorption :
Well absorbed
▧ Volume of Distribution :
* 30.8 ± 7.5 L [CKD Stage 5-HD] * 34.9 ± 9.5 L [CKD Stage 5-PD] * 23.8 L [healthy subjects]
▧ Protein binding :
99.8% (bound to plasma proteins)
▧ Metabolism :
Metabolized by multiple hepatic and non-hepatic enzymes, including mitochondrial CYP24, as well as CYP3A4 and UGT1A4
▧ Route of Elimination :
Paricalcitol is excreted primarily by hepatobiliary excretion.
▧ Half Life :
4 to 6 hours
▧ Clearance :
* 1.49 +/- 0.60 L/h [chronic kidney disease Stage 5 with hemodialysis] * 1.54 +/- 0.95 L/h [chronic kidney disease Stage 5with peritoneal dialysis]
Chỉ Định : For treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD) Stage 3 and 4
Tương Tác Thuốc :
  • Cholecalciferol Vitamin D analogs may enhance the adverse/toxic effect of other Vitamin D analogs. Avoid combined use of multiple vitamin D analogs (at pharmacologic doses). Prescribing information for calcitriol, doxercalciferol, paricalcitol, and alfacalcidol each specifically cautions against such combined use. Though not specified in the prescribing information for calcipotriene, cholecalciferol, and ergocalciferol, each contains warnings regarding the potential for vitamin D toxicity.
  • Colesevelam Bile acid sequestrants such as colesevelam may decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (e.g., cholestyramine). Monitor plasma calcium concentrations in patients receiving combined therapy with these agents. This is particularly important in patients receiving higher doses of a bile acid sequestant (i.e., 30 g/day or more of cholestyramine or equivalent) or in patients experiencing bile acid sequestrant-induced steatorrhea. Specific recommendations regarding the separation of administration of these agents are not defined; however, it would seem prudent to separate the administration of these agents by several hours to minimize the potential risk of interaction. Similar precautions do not apply to parenterally administered vitamin D analogs.
Liều Lượng & Cách Dùng : Solution - Intravenous
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Zemplar 1 mcg capsule
    Giá bán buôn : USD >9.39
    Đơn vị tính : capsule
  • Biệt dược thương mại : Zemplar 2 mcg/ml vial
    Giá bán buôn : USD >11.22
    Đơn vị tính : ml
  • Biệt dược thương mại : Zemplar 2 mcg capsule
    Giá bán buôn : USD >18.79
    Đơn vị tính : capsule
  • Biệt dược thương mại : Zemplar 5 mcg/ml vial
    Giá bán buôn : USD >28.03
    Đơn vị tính : ml
  • Biệt dược thương mại : Zemplar 4 mcg capsule
    Giá bán buôn : USD >37.58
    Đơn vị tính : capsule
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Zemplar
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00910
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5281104
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505780
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C08127
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00930
ChemSpider
http://www.chemspider.com/Chemical-Structure.4444552.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0074-4637-01
PharmGKB
http://www.pharmgkb.org/drug/PA450798
RxList
http://www.rxlist.com/cgi/generic4/zemplar_caps.htm
Drugs.com
http://www.drugs.com/cdi/paricalcitol.html
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