Paricalcitol
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| Systematic (IUPAC) name | |
| (1R,3R,7E,17β)-17-[(1R,2E,4S)-5-hydroxy-1,4,5-trimethylhex-2-en-1-yl]-9,10-secoestra-5,7-diene-1,3-diol | |
| Clinical data | |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a682335 |
| Pregnancy cat. | C |
| Legal status | ? |
| Routes | Oral, Intravenous |
| Pharmacokinetic data | |
| Bioavailability | N/A |
| Half-life | 5 to 7 hours in healthy subjects |
| Excretion | Biliary |
| Identifiers | |
| CAS number | 131918-61-1  |
| ATC code | H05BX02 |
| PubChem | CID 5281104 |
| DrugBank | DB00910 |
| ChemSpider | 4444552 |
| UNII | 6702D36OG5 |
| KEGG | D00930  |
| ChEBI | CHEBI:7931 |
| ChEMBL | CHEMBL1200622 |
| Synonyms | (1R,3S)-5-[2-[(1R,3aR,7aS)-1-[(2R,5S)-6-hydroxy-5,6-dimethyl-3E-hepten-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-cyclohexane-1,3-diol |
| Chemical data | |
| Formula | C27H44O3 |
| Mol. mass | 416.636 g/mol |
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Paricalcitol (marketed by Abbott Laboratories under the trade name Zemplar) is a drug used for the prevention and treatment of secondary hyperparathyroidism (excessive secretion of parathyroid hormone) associated with chronic renal failure. Chemically, it is 19-nor-1,25-(OH)2-vitamin D2 or 19-nor-1,25-dihydroxyvitamin D2, being an analog of 1,25-dihydroxyergocalciferol, the active form of vitamin D2.
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[edit] Mechanism of action
Like 1,25-dihydroxyergocalciferol, paricalcitol acts as an agonist for the vitamin D receptor and thus lowers the blood parathyroid hormone level.
[edit] Studies
In three placebo-controlled studies, chronic renal failure patients treated with paricalcitol achieved a mean parathyroid hormone (PTH) reduction of 30% in six weeks. Additionally there was no difference in incidence of hypercalcemia or hyperphosphatemia when compared to placebo.[1]
A double-blind randomised study with 263 dialysis patients showed a significant advantage over calcitriol (also known as activated vitamin D3; a similar molecule to 1,25-dihydroxyergocalciferol, adding a methyl group on C24 and lacking a double-bond in the C22 position). After 18 weeks, all patients in the paricalcitol group had reached the target parathormone level of 100 to 300 pg/ml, versus none in the calcitriol group.[2]
Combination therapy with paricalcitol and trandolapril has been found to reduce fibrosis in obstructive uropathy.[3]
[edit] Pharmacokinetics
Within two hours after administering paricalcitol intravenous doses ranging from 0.04 to 0.24 µg/kg, concentrations of paricalcitol decreased rapidly; thereafter, concentrations of paricalcitol declined log-linearly. No accumulation of paricalcitol was observed with multiple dosing.[4]
[edit] Side effects
Paricalcitol has been evaluated for safety in clinical studies in 454 chronic renal failure stage 5 patients. In four, placebo-controlled, double-blind, multicenter studies, discontinuation of therapy due to any adverse event occurred in 6.5% of 62 patients treated with paricalcitol, and 2.0% of 51 patients treated with placebo for 1 to 3 months.
Potential adverse events of paricalcitol injection are, in general, similar to those encountered with excessive vitamin D intake. Signs and symptoms of vitamin D intoxication associated with hypercalcemia include:
Early: Weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain, and metallic taste.
Late: Anorexia, weight loss, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated blood urea nitrogen, hypercholesterolemia, elevated AST and ALT, ectopic calcification, hypertension, cardiac arrhythmias, somnolence, death, and rarely, overt psychosis.[4]
[edit] References
- ^ "Zemplar: Drug Information"
- ^ Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel 2005/2006 (in German).
- ^ Tan, X; He, W; Liu, Y (2009). "Combination therapy with paricalcitol and trandolapril reduces renal fibrosis in obstructive nephropathy". Kidney international 76 (12): 1248–57. doi:10.1038/ki.2009.346. PMID 19759524.
- ^ a b Rxlist: Zemplar
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