Paricalcitol is a drug used for the prevention and treatment of secondary hyperparathyroidism

Secondary hyperparathyroidism

Secondary hyperparathyroidism refers to the excessive secretion of parathyroid hormone by the parathyroid glands in response to hypocalcemia and associated hypertrophy of the glands. This disorder is especially seen in patients with chronic renal failure...

 (excessive secretion of parathyroid hormone

Parathyroid hormone

Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...

) associated with chronic renal failure

Chronic renal failure

Chronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...

. Chemically, it is 19-nor-1,25-(OH)₂-vitamin D₂ or 19-nor-1,25-dihydroxyvitamin D₂, being an analog

Analog (chemistry)

In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...

 of 1,25-dihydroxyergocalciferol, the active form of vitamin D₂.

Mechanism of action

Like 1,25-dihydroxyergocalciferol, paricalcitol acts as an agonist for the vitamin D receptor and thus lowers the blood parathyroid hormone

Parathyroid hormone

Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...

 level.

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.

A double-blind randomised study with 263 dialysis patients showed a significant advantage over calcitriol

Calcitriol

Calcitriol , also called 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3, is the hormonally active form of vitamin D with three hydroxyl groups...

 (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.

Combination therapy with paricalcitol and trandolapril

Trandolapril

Trandolapril is an ACE inhibitor used to treat high blood pressure, it may also be used to treat other conditions.It is marketed by Abbott Laboratories with the brand name Mavik.- Pharmacology :...

 has been found to reduce fibrosis

Fibrosis

Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...

 in obstructive uropathy

Obstructive uropathy

Obstructive uropathy is a structural or functional hindrance of normal urine flow, sometimes leading torenal dysfunction .It is a very broad term, and does not imply a location or etiology.-Causes:...

.

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.

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

Constipation

Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...

, muscle pain, bone pain, and metallic taste.

Late: Anorexia

Anorexia (symptom)

Anorexia is the decreased sensation of appetite...

, weight loss, conjunctivitis

Conjunctivitis

Conjunctivitis refers to inflammation of the conjunctiva...

 (calcific), pancreatitis

Pancreatitis

Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...

, photophobia

Photophobia

Photophobia is a symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical photosensitivity of the eyes, though the term...

, rhinorrhea

Rhinorrhea

Rhinorrhea or rhinorrhoea is a condition where the nasal cavity is filled with a significant amount of mucous fluid. The condition, commonly known as "runny nose", occurs relatively frequently and is not usually considered dangerous. Rhinorrhea is a common symptom of allergies or certain diseases,...

, pruritus, hyperthermia, decreased libido, elevated blood urea nitrogen

Blood urea nitrogen

The blood urea nitrogen test is a measure of the amount of nitrogen in the blood in the form of urea, and a measurement of renal function. Urea is a by- product from metabolism of proteins by the liver and is removed from the blood by the kidneys.-Physiology:The liver produces urea in the urea...

, hypercholesterolemia, elevated AST

Aspartate transaminase

Aspartate transaminase , also called aspartate aminotransferase or serum glutamic oxaloacetic transaminase , is a pyridoxal phosphate -dependent transaminase enzyme . AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in...

 and ALT

Alanine transaminase

Alanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....

, ectopic calcification

Ectopic calcification

Ectopic calcification is a pathologic deposition of calcium salts in tissues. This can be a symptom of hyperphosphatemia.-References:*...

, hypertension

Hypertension

Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, cardiac arrhythmias, somnolence, death, and rarely, overt psychosis

Psychosis

Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...

.