CABERGOLINE

Obstet Gynecol. 2013 Aug;122(2 Pt 2):485-7. doi: 10.1097/AOG.0b013e31829e398a.

http://www.ncbi.nlm.nih.gov/pubmed/23884269
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Woo I, Ehsanipoor RM.
Source
Department of Gynecology and Obstetrics and Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
BACKGROUND:
Cushing disease during pregnancy is rare and is associated with significant maternal and fetal morbidity and mortality. Transsphenoidal pituitary surgery is the first-line therapy; however, in cases of failed surgery or in patients who are not surgical candidates, medical therapy has been used to control symptoms.
CASE:
A 29-year-old woman with Cushing disease and a noncurative transsphenoidal pituitary surgery was successfully treated with cabergoline, a dopamine agonist. After approximately 1 year of therapy, she became pregnant. She was maintained on high-dose cabergoline throughout her pregnancy and had an uncomplicated antenatal course. She went into spontaneous labor at 38 weeks of gestation and delivered a healthy female neonate.
CONCLUSION:
Cabergoline can be used to manage Cushing disease successfully during pregnancy with an opportunity for a favorable outcome.

Cabergoline (brand names Dostinex and Cabaser), an ergot derivative, is a potent dopamine receptor agonist on D₂ receptors. In vitro, rat studies show cabergoline has a direct inhibitory effect on pituitary lactotroph (prolactin) cells.^[1] It is frequently used as a first-line agent in the management of prolactinomas due to higher affinity for D₂ receptor sites, less severe side effects, and more convenient dosing schedule than the older bromocriptine.

History

Cabergoline was invented by scientists working for the Italian drug company Farmitalia-Carlo Erba SpA in Milan in 1981/82,^[2] who were experimenting with semisynthetic derivatives of the ergot alkaloids. Farmitalia-Carlo Erba was acquired by Pharmacia in 1992, which in turn was acquired by Pfizer in 2002. The drug was approved by the FDA on December 23, 1996. It went generic in late 2005 following US patent expiration.

Intellectual property

Farmitalia filed a patent application for Cabergoline in 1982, and U.S. Patent 4,526,892 issued in July 1985.

Pharmacology

Although cabergoline is commonly described principally as a dopamine D₂ receptor agonist, it also possesses significant affinity for the D₃, D₄, 5-HT_1A, 5-HT_2A, 5-HT_2B, 5-HT_2C, α_2B– receptors, and moderate/low affinity for the D₁ and 5-HT₇ receptors. Cabergoline functions as an agonist at all of these receptors except for 5-HT₇ and α_2B–, where it acts as an antagonist.^[3]

Following a single oral dose, resorption of cabergoline from the gastrointestinal (GI) tract is highly variable, typically occurring within 0.5 to 4 hours. Ingestion with food does not alter its absorption rate. Human bioavailability has not been determined since the drug is intended for oral use only. In mice and rats the absolute bioavailability has been determined to be 30 and 63 percent, respectively. Cabergoline is rapidly and extensively metabolized in the liver and excreted in bile and to a lesser extent in urine. All metabolites are less active than the parental drug or inactive altogether. The human elimination half-life is estimated to be 63 to 68 hours in patients with Parkinson’s disease and 79 to 115 hours in patients with pituitary tumors. Average elimination half-life is 80 hours.

The therapeutic effect in treatment of hyperprolactinemia will typically persist for at least 4 weeks after cessation of treatment.

Mechanism of action

Cabergoline is a long-acting dopamine D₂ receptor agonist and in vitro rat studies show a direct inhibitory effect on the prolactin secretion in the pituitary’s lactotroph cells. Cabergoline decreased serum prolactin levels in reserpinized rats.

Receptor binding studies indicate a low affinity for dopamine D₁ receptors, α₁-adrenergic receptors, and α₂-adrenergic receptors.^[1]

• 1  Dostinex at www.rxlist.com”. Retrieved 2007-04-27.
• 2 US Patent 4526892 – Dimethylaminoalkyl-3-(ergoline-8′.beta.carbonyl)-ureas
• 3  Sharif NA, McLaughlin MA, Kelly CR, Katoli P, Drace C, Husain S, Crosson C, Toris C, Zhan GL, Camras C (March 2009). “Cabergoline: Pharmacology, ocular hypotensive studies in multiple species, and aqueous humor dynamic modulation in the Cynomolgus monkey eyes”. Experimental Eye Research 88 (3): 386–97. doi:10.1016/j.exer.2008.10.003. PMID 18992242.
• 4  National Institute ofMental Health. PDSD Ki Database (Internet) [cited 2013 Jul 24]. ChapelHill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php
• 5   Sayyah-Melli, M; Tehrani-Gadim, S; Dastranj-Tabrizi, A; Gatrehsamani, F; Morteza, G; Ouladesahebmadarek, E; Farzadi, L; Kazemi-Shishvan, M (2009). “Comparison of the effect of gonadotropin-releasing hormone agonist and dopamine receptor agonist on uterine myoma growth. Histologic, sonographic, and intra-operative changes”. Saudi medical journal 30 (8): 1024–33. PMID 19668882. edit

6  Sankaran, S.; Manyonda, I. (2008). “Medical management of fibroids”. Best Practice & Research Clinical Obstetrics & Gynaecology 22 (4): 655. doi:10.1016/j.bpobgyn.2008.03.001. PMID 18468953. edit http://www.britishfibroidtrust.org.uk/journals/bft_Sankaran.pdf

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