|Systematic (IUPAC) name|
|Half-life||5 to 7 hours in healthy subjects|
|Mol. mass||416.636 g/mol|
| (what is this?)
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 (Ergocalciferol).
Mechanism of action
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.
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.
Forty-eight week therapy with paricalcitol did not alter left ventricular mass index or improve certain measures of diastolic dysfunction in 227 patients with chronic kidney disease.
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.
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:
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.
- "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.
- Thadhani, R; Appelbaum, E; Pritchett, Y; Chang, Y; Wenger, J; Tamez, H; Bhan, I; Agarwal, R et al. (2012). "Vitamin D Therapy and Cardiac Structure and Function in Patients With Chronic Kidney Disease - The PRIMO Randomized Controlled Trial". JAMA 307 (7): 674–684. doi:10.1001/jama.2012.120. PMID 22337679.
- Rxlist: Zemplar