Paricalcitol

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 1 Mechanism of action 2 Studies 3 Pharmacokinetics 4 Side effects 5 References

[edit] Mechanism of action

Like calcitriol, paricalcitol acts as an agonist for the calcitriol receptor and thus lowers the blood parathormone level.

[edit] 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]

[edit] 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]

[edit] 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]

[edit] References

v • d • e Vitamins (A11) Fat soluble A Retinol · β-Carotene · Tretinoin · α-Carotene D D2 (Ergosterol, Ergocalciferol)  · D3 (7-Dehydrocholesterol, Previtamin D3, Cholecalciferol, 25-hydroxycholecalciferol, Calcitriol (1,25-dihydroxycholecalciferol), Calcitroic acid) D4 (Dihydroergocalciferol)  · D5  · D analogues (Dihydrotachysterol, Calcipotriol, Tacalcitol, Paricalcitol) E Tocopherol (Alpha, Beta, Gamma, Delta) · Tocotrienol · Tocofersolan K Naphthoquinone · Phylloquinone/K1 · Menatetrenone/K2 · Menadione/K3 Water soluble B B1 (Thiamine) · B2 (Riboflavin) · B3 (Niacin, Nicotinamide) · B5 (Pantothenic acid, Dexpanthenol, Pantethine) · B6 (Pyridoxine, Pyridoxal phosphate, Pyridoxamine) B7 (Biotin) · B9 (Folic acid, Dihydrofolic acid, Folinic acid) · B12 (Cyanocobalamin, Hydroxocobalamin, Methylcobalamin, Cobamamide)  · Choline C Ascorbic acid  · Dehydroascorbic acid see also: enzyme cofactors, enzymes, Multivitamins

v • d • e Calcium homeostasis (H05) Parathyroid hormones and analogues Teriparatide Anti-parathyroid agents Calcitonin/Elcatonin • Cinacalcet • Vitamin D analogues (Doxercalciferol, Paricalcitol)