Paricalcitol
From Wikipedia, the free encyclopedia
| 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 | |
| Identifiers | |
| CAS number | 131918-61-1 |
| ATC code | H05BX02 |
| PubChem | 5281104 |
| Chemical data | |
| Formula | C27H44O3 |
| Mol. mass | 416.636 g/mol |
| 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 |
| Pharmacokinetic data | |
| Bioavailability | N/A |
| Metabolism | ? |
| Half life | 5 to 7 hours in healthy subjects |
| Excretion | Biliary |
| Therapeutic considerations | |
| Pregnancy cat. | C |
| Legal status | |
| Routes | Oral, Intravenous |
Paricalcitol (marketed by Abbott Laboratories under the trade name Zemplar) is an analog of calcitriol, the active form of vitamin D. It is used for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure.
Contents |
Mechanism of action
Like calcitriol, paricalcitol acts as an agonist for the calcitriol receptor and thus lowers the blood parathormone level.
Studies
In three placebo-controlled studies, chronic renal failure patients treated with Zemplar 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. 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]
Pharmacokinetics
Within two hours after administering Zemplar 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]
Side effects
Zemplar has been evaluated for safety in clinical studies in 454 CKD (chronic kidney 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 Zemplar, and 2.0% of 51 patients treated with placebo for 1 to 3 months.
Potential adverse events of Zemplar 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.[5]
References
- ^ "Zemplar: Drug Information"
- ^ Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel 2005/2006 (in German).
- ^ Tan, X; He, W; Liu, Y (2009). [Expression error: Missing operand for > "Combination therapy with paricalcitol and trandolapril reduces renal fibrosis in obstructive nephropathy"]. Kidney international. doi:. PMID 19759524.
- ^ "Zemplar: Pharmacology"
- ^ "Zemplar Injection: Side Effects and Drug Interactions"
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