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Cabergoline

Central Nervous System Drugs
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Brands

Dostinex
Galastop (Europe)
Cabasar

Availability

Tablets: 0.5mg (available as Dostinex)
Capsules: in a variety of strengths
Cabergoline oil suspension 17.5 mcg/mL to 500 mcg/mL ; 1 mg/mL (can be made up in flavors) http://www.wedgewoodpetrx.com/items/cabergoline-oral-oil-suspension.html
Suspensions may also be made up in 2mg/mL concentrations
*Note: Galastop (European brand name)comes in a concentration of 50ug/mL (0.05mg/ml). To achieve the desired therapeutic dose for rats would require a large volume to be given. If possible, compounding a suspension from tablets for human’s would provide a more manageable dosing volume when giving to rats.

Pharmacology

Cabergoline, similar to bromocriptine and pergolide, is an ergot derivative doapamine receptor agonist. However, cabergoline has a greater affinity for D2 receptors in the pituitary. It is shown to be more effective than bromocriptine in inducing complete biochemical response and clinical efficacy.
Cabergoline has both a longer half-life and duration of action compared with bromocriptine or pergolide. This lends itself to once every third day dosing, in the pet rat, compared to the once every 24 hour dosing required with bromocriptine or pergolide.

The secretion of prolactin (hormone) by the anterior pituitary is primarily under hypothalamic inhibitory control, which is most likely exerted through the release of dopamine by tuberoinfundibular neurons. Dopamine receptor agonists are able to lower circulating prolactin levels and reduce the size of pituitary prolactin-secreting tumors.

In studies done, cabergoline was shown to exert a direct inhibitory effect on the secretion of prolactin by rat pituitary lactotrophs, thereby decreasing serum prolactin levels. Studies also indicate that cabergoline has a low affinity for dopamine D1, α1- and α2-adrenergic, and 5-HT1- and 5-HT2-serotonin receptors.
Cabergoline is shown to be more effective in those patients resistant to, or poorly responsive to, bromocriptine.

Cabergoline is well absorbed orally; however a significant fraction of the dose given undergoes a first-pass effect. The elimination half-life following a single dose of cabergoline , in rats, is approximately 60 hours (1). The prolonged prolactin-lowering effect of cabergoline in the target organ is most likely due to its slow elimination and long half-life.

Cabergoline is widely distributed into tissue as indicated by high concentrations of the drug in the pituitary compared to serum. Studies in rats also reflected significant concentrations of cabergoline in the mammary glands and uterine wall, as well as being able to cross the placenta {2}.

Cabergoline is rapidly and extensively metabolized in the liver and excreted in bile and to a lesser extent in urine. Less than 4% of the dose was found to be excreted unchanged in the urine.

An important note: because cabergoline has been shown to cause spontaneous abortion in dogs and cats, and because cabergoline is able to suppress prolactin, it is recommended that it not be administered to pregnant or lactating rats.

Indications

For the treatment of prolactin-secreting pituitary tumors.

Or, where there has been removal of existing benign (adenoma) mammary tumors, the use of a prolactin secretion inhibitor such as cabergoline may be beneficial in the prevention of new benign tumor growth

Drug Interactions or Contraindications

Avoid administering cabergoline concurrently with D2-antagonists, such as phenothiazines, butyrophenones, thioxanthenes, or metoclopramide since efficacy could be reduced.

Plasma levels of cabergoline may increase when co-administered with erythromycin or ketoconazole.

Adverse Reactions

CNS:  lethargy

CV:  low blood pressure, abnormal/irregular heart beat, valvulopathy, pericardial fibrosis

Respiratory:  nasal congestion, pleural/pulmonary fibrosis

GI:  nausea, decreased appetite, dry mouth, diarrhea, constipation

Skin:  pruitus (itching)

Other:  behavioral changes

Dosage Recommendations

*Note: if impaired liver function is thought to be present the reduction of dosage may need to be considered.

0.6 mg/kg [0.27 mg/lb], PO, q 72 hr (4)

Considerations

  • Food did not alter cabergoline kinetics, and is therefore recommended to be given with food.
  • Protect from light and store at controlled room temperature 20° to 25°C (68° to 77°F). Do not refrigerate. It is thought that efficacy may persist for up to one month with proper storage.
  • It is recommended that the drug be compounded in a lipid-base since the drug degrades becoming unstable in “aqueous” suspensions.  27
  • Note that compounding pharmacies are able to make cabergoline suspensions in appealing flavors and in concentrations small enough for dosing in the rat.
Reference
  1. Dostinex® Cabergoline 0.5mg tablet. (2009, July 1). Medsafe. Retrieved September 9, 2012, from www.medsafe.govt.nz/profs/datasheet/d/Dostinextab.pdf
  2. Product Monograph: PRDostinex*(cabergoline). (2009, May 15). Pfizer.ca. Retrieved September 9, 2012, from www.pfizer.ca/en/our_products/products/monograph/159
  3. Beltrame, D., Longo, M., & Mazué, G. (1996). Reproductive toxicity of cabergoline in mice, rats, and rabbits. Reprod Toxicol, 10(6), 471-83.
  4. Mayer, J., Sato, A., Kiupel, M., DeCubellis, J., & Donnelly, T. (2011). Extralabel use of cabergoline in the treatment of a pituitary adenoma in a rat. J Am Vet Med Assoc., 239(5), 656-60.
  5. Dostinex package insert (Pharmacia & Upjohn—US), Rev 12/1996, Rec 2/1997.
  6. Dall’Ara, A., Lima, L., Cocchi, D., Salle, E. D., Cancio, E., Devesa, J., Müller, E. (1988). Inhibitory effect of cabergoline on the development of estrogen-induced prolactin-secreting adenomas of the pituitary. Eur J Pharmacol., 151(1), 97-102.

Posted on September 4, 2012, 12:06, Last updated on June 20, 2013, 14:42 | Central Nervous System Drugs



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