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药品详细

Paricalcitol(帕立骨化醇)

化学结构式图
中文名
帕立骨化醇
英文名
Paricalcitol
分子式
C27H44O3
化学名
(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
分子量
Average: 416.6365
Monoisotopic: 416.329045274
CAS号
131918-61-1
ATC分类
H05B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

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.

生产厂家
  • Abbott laboratories
  • Abbott laboratories pharmaceutical products div
封装厂家
参考
Synthesis Reference Not Available
General Reference Not Available
剂型
规格
化合物类型
Type small molecule
Classes
  • Alcohols and Polyols
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Alcohols and Polyols
适应症
药理
Indication For treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD) Stage 3 and 4
Pharmacodynamics 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).
Mechanism of action 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.
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]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
logP 4.5 Not Available
Predicted Properties
Property Value Source
water solubility 6.80e-03 g/l ALOGPS
logP 5.27 ALOGPS
logP 4.26 ChemAxon
logS -4.8 ALOGPS
pKa (strongest acidic) 14.81 ChemAxon
pKa (strongest basic) -1 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 60.69 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 127.95 ChemAxon
polarizability 51.11 ChemAxon
药物相互作用
Drug Interaction
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.
食物相互作用
Not Available

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