请输入您要查询的百科知识：

　

词条 Paricalcitol
释义

  1. Medical uses

  2. Adverse effects

     Contraindications  Interactions  Overdose 

  3. Mechanism of action

  4. Pharmacokinetics

  5. References

{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 445909355
| 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
| image = Paricalcitol.svg
| width = 200px
| image2 = Paricalcitol3Dan.gif
| width2 = 200px
| tradename = Zemplar
| Drugs.com = {{drugs.com|monograph|paricalcitol}}
| MedlinePlus = a682335
| pregnancy_AU = C
| pregnancy_US = C
| pregnancy_category =
| legal_AU = S4
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = Rx-only
| legal_status =
| routes_of_administration = Oral, Intravenous
| bioavailability = 72%[1]
| protein_bound = 99.8%[1]
| metabolism = Hepatic[1]
| elimination_half-life = 14-20 hours[1]
| excretion = Faeces (74%), urine (16%)[1]
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 131918-61-1
| ATC_prefix = H05
| ATC_suffix = BX02
| ATC_supplemental =
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 7931
| PubChem = 5281104
| IUPHAR_ligand = 2791
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB00910
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4444552
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6702D36OG5
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D00930
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1200622
| chemical_formula =
| C=27 | H=44 | O=3
| molecular_weight = 416.636 g/mol
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C27H44O3/c1-18(8-9-19(2)26(3,4)30)24-12-13-25-21(7-6-14-27(24,25)5)11-10-20-15-22(28)17-23(29)16-20/h8-11,18-19,22-25,28-30H,6-7,12-17H2,1-5H3/b9-8+,21-11+/t18-,19+,22-,23-,24-,25+,27-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = BPKAHTKRCLCHEA-UBFJEZKGSA-N
| 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
}}

Paricalcitol (chemically it is 19-nor-1,25-(OH)2-vitamin D2. 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. It is an analog of 1,25-dihydroxyergocalciferol, the active form of vitamin D2 (ergocalciferol).

It was patented in 1989 and approved for medical use in 1998.[1]

Medical uses

Its primary use in medicine is in the treatment of secondary hyperparathyroidism associated with chronic kidney disease.[2] 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.[3] 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.[4] Combination therapy with paricalcitol and trandolapril has been found to reduce fibrosis in obstructive uropathy.[5] 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.[6]

Adverse effects

Adverse effects by frequency:[7][2][8][9]
Very common (>10% frequency):
  • Nausea
Common (1-10% frequency):{{div col|colwidth=18em}}
  • Diarrhoea†
  • Oedema
  • Allergic reaction
  • Arthritis
  • Dizziness†
  • Stomach discomfort‡
  • Gastroesophageal reflux disease†
  • Acne†
  • Hypercalcaemia†
  • Hypocalcaemia†
  • Hyperphosphataemia
  • Decreased appetite†
  • Headache
  • Breast tenderness†
  • Taste changes
  • Hypoparathyroidism
  • Vertigo
  • Rash‡
{{div col end}}Uncommon (0.1-1% frequency):{{div col|colwidth=18em}}
  • Abnormal hepatic enzymes‡
  • Constipation‡
  • Dry mouth‡
  • Itchiness‡
  • Hives
  • Hypersensitivity‡
  • Muscle spasms‡
  • Bleeding time prolonged
  • Aspartate aminotransferase increased
  • Laboratory test abnormal
  • Weight loss
  • Elevated blood creatinine
  • Cardiac arrest
  • Arrhythmia
  • Atrial flutter
  • Anaemia
  • Leucopenia
  • Lymphadenopathy
  • Coma
  • Stroke
  • Transient ischemic attack
  • Fainting
  • Myoclonus
  • Hypoaesthesia
  • Paraesthesia
  • Glaucoma
  • Conjunctivitis
  • Ear disorder
  • Pulmonary oedema
  • Asthma
  • Shortness of breath
  • Nose bleed
  • Cough
  • Rectal haemhorrhage
  • Colitis
  • Gastritis
  • Indigestion
  • Difficulty swallowing
  • Gastrointestinal disorder
  • Gastrointestinal haemorrhage
  • Bullous dermatitis
  • Hair loss
  • Hirsutism
  • Hyperhidrosis
  • Joint pain
  • Joint stiffness
  • Back pain
  • Muscle twitching
  • Muscle aches
  • Hyperparathyroidism
  • Hyperkalaemia
  • Hypocalcemia
  • Breast cancer
  • Sepsis
  • Pneumonia
  • Infection
  • Pharyngitis
  • Vaginal infection
  • Influenza
  • High blood pressure
  • Hypotension
  • Gait disturbance
  • Injection site pain
  • Fever
  • Chest pain
  • Condition aggravated
  • Muscle weakness
  • Malaise
  • Thirst
  • Breast pain
  • Impotence
  • Confusional state
  • Delirium
  • Depersonalization
  • Agitation
  • Insomnia
  • Nervousness
{{div col end}}

‡ These are adverse effects only seen in patients with grade 3 or 4 chronic kidney disease.

† These are adverse effects only seen in patients with grade 5 chronic kidney disease.

Contraindications

Contraindications include:[9]

  • Vitamin D intoxication
  • Hypercalcaemia
  • Hypersensitivity to paricalcitol or any of its excipients

whereas cautions include:[7]

  • Impaired liver function
  • It is also advised that physicians regularly monitor their patients' calcium and phosphorus levels.

Interactions

Drugs that may interact with paricalcitol include:[7][9]

{{div col|colwidth=30em}}
  • Ketoconazole, as it may interfere with paricalcitol's metabolism in the liver.
  • Digitoxin, hypercalcaemia due to any cause can exacerbate the toxicity of digitoxin.
  • Thiazide diuretics or calcium supplements as hypercalcaemia may be induced by this combination
  • Magnesium-containing products such as antacids may increase the risk of hypermagnesemia.
  • Aluminium-containing products such as antacids may increase the risk of aluminium toxicity.
  • Drugs that interfere with the absorption of fat-soluble vitamins, such as cholestyramine may interfere with the absorption of paricalcitol.
{{div col end}}

Overdose

Electrolyte abnormalities (e.g. hypercalcaemia and hyperphosphataemia) are common overdose symptoms.[9] Treatment is mostly supportive, with particular attention being paid to correcting electrolyte anomalies and reducing intake of calcium in both the form of supplementation and diet.[9] As it is so heavily bound to plasma proteins haemodialysis is unlikely to be helpful in cases of overdose.[9]

Early symptoms of overdose can include:[9]

{{div col|colwidth=18em}}
  • Weakness
  • Headache
  • Somnolence
  • Nausea
  • Vomiting
  • Dry mouth
  • Constipation
  • Muscle pain
  • Bone pain
  • Metallic taste in the mouth.
{{div col end}}

It is worth noting, however, that may of these symptoms are also indicative of kidney failure and hence may be masked by the patient's condition.[9]

Late symptoms of overdose include:

{{div col|colwidth=18em}}
  • Loss of appetite
  • Weight loss
  • Conjunctivitis (calcific)
  • Pancreatitis
  • Photophobia
  • Rhinorrhoea
  • Pruritus
  • Hyperthermia
  • Decreased libido
  • Elevated BUN
  • Hypercholesterolaemia
  • Elevated AST and ALT
  • Ectopic calcification
  • Hypertension
  • Cardiac arrhythmias
  • Somnolence
  • Death
  • Psychosis (rare)
{{div col end}}

Mechanism of action

{{clear left}}

Like 1,25-dihydroxyergocalciferol, paricalcitol acts as an agonist at the vitamin D receptor and thereby lowers parathyroid hormone levels in the blood.[7]

Pharmacokinetics

The plasma concentration of paricalcitol decreases rapidly and log-linearly within two hours after initial intravenous administration. Therefore, it is not expected to accumulate with multiple dosing, since paricalcitol is usually given no more frequently than every other day (3 times per week).[10][11]

References

1. ^{{cite book |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=452 |url=https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA452 |language=en}}
2. ^1 {{cite book | editor = Rossi, S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }}
3. ^"Zemplar: Drug Information"
4. ^Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel 2005/2006 (in German).
5. ^{{cite journal|doi=10.1038/ki.2009.346|pmid=19759524|year=2009|last1=Tan|first1=X|last2=He|first2=W|last3=Liu|first3=Y|title=Combination therapy with paricalcitol and trandolapril reduces renal fibrosis in obstructive nephropathy|volume=76|issue=12|pages=1248–57|journal=Kidney International}}
6. ^{{cite journal|doi=10.1001/jama.2012.120|pmid=22337679|year=2012|last1=Thadhani|first1=R|last2=Appelbaum|first2=E|last3=Pritchett|first3=Y|title=Vitamin D Therapy and Cardiac Structure and Function in Patients With Chronic Kidney Disease - The PRIMO Randomized Controlled Trial|volume=307|issue=7|pages=674–684|journal=JAMA|last4=Chang|first4=Y|last5=Wenger|first5=J|last6=Tamez|first6=H|last7=Bhan|first7=I|last8=Agarwal|first8=R|last9=Zoccali|first9=C|last10=Wanner|first10=Christoph|last11=Lloyd-Jones|first11=Donald|last12=Cannata|first12=Jorge|last13=Thompson|first13=B. Taylor|last14=Andress|first14=Dennis|last15=Zhang|first15=Wuyan|last16=Packham|first16=David|last17=Singh|first17=Bhupinder|last18=Zehnder|first18=Daniel|last19=Shah|first19=Amil|last20=Pachika|first20=Ajay|last21=Manning|first21=Warren J.|last22=Solomon|first22=Scott D.|display-authors=8}}
7. ^1 2 3 4 5 6 7 8 {{cite web|title=Zemplar (paricalcitol) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|accessdate=26 January 2014|url=http://reference.medscape.com/drug/zemplar-paricalcitol-342830#showall}}
8. ^{{cite web|title=PARICALCITOL capsule, liquid filled [Teva Pharmaceuticals USA Inc]|work=DailyMed|publisher=Teva Pharmaceuticals USA Inc|accessdate=26 January 2014|url=http://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=c233cba2-d645-426c-9e4d-ef616edc7903&type=pdf&name=c233cba2-d645-426c-9e4d-ef616edc7903|format=PDF|date=September 2013}}
9. ^1 2 3 4 5 6 7 {{cite web|title=Zemplar Soft Capsules 1 mcg - Summary of Product Characteristics|publisher=AbbVie Limited|work=electronic Medicines Compendium|date=15 April 2013|accessdate=26 January 2014|url=http://www.medicines.org.uk/emc/medicine/20464/SPC/Zemplar+Soft+Capsules+1+mcg/}}
10. ^Rxlist: Zemplar
11. ^{{cite book|title=Zemplar (paricalcitol) [prescribing information].|date=October 1, 2015|publisher=AbbVie Inc.|location=North Chicago, IL|accessdate=December 12, 2016}}
{{Vitamins}}{{Calcium homeostasis}}{{Vitamin D receptor modulators}}

2 : Secosteroids|Vitamin D
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/9/21 1:31:34