Some data on catechol O-methyltransferase inhibitors and dopamine agonists all refer to in vitro studies of the drugs. As for in vivo situations, for example, a synthetic ergoline dopamine agonist cabergoline has a high affinity for D(2) receptors indicated for use in both early and advanced Parkinson's disease and in hyperprolactinaemic disorders. Following oral administration, peak plasma concentrations of cabergoline are reached within 2-3 hours. Over the 0.5-7mg dose range, cabergoline shows linear pharmacokinetics in healthy adult volunteers and parkinsonian patients. Cabergoline is moderately bound (around 40%) to human plasma proteins in a concentration-independent manner; concomitant administration of highly protein-bound drugs is unlikely to affect its disposition. The absolute bioavailability of cabergoline is unknown. Cabergoline is extensively metabolised by the liver, predominantly via hydrolysis of the acylurea bond of the urea moiety. Cytochrome P450-mediated metabolism appears to be minimal. The major metabolites identified thus far do not contribute to the therapeutic effect of cabergoline. A significant fraction of the administered dose undergoes a first-pass effect. Less than 4% is excreted unchanged in the urine. The elimination half-life of cabergoline estimated from urinary data of healthy subjects ranges between 63 and 109 hours. Mild to moderate renal and hepatic impairment, administration of food and the use of concomitant antiparkinsonian medications, such as levodopa and selegiline, have no effect on the pharmacokinetics of cabergoline.
Some antiparkinsonian medications may have drug-drug interactions, like Selegiline (MAO-BI). Cabergoline is not a highly selective D2 agonist, since it also has some affinity for serotonin and D3 receptors as well, and is the first line drug for the treatment of prolactinomas. It is not a good agent for monotherapy in PD in the late phase, although being a long acting D2 agonist.
Since it is an ergot alkaloid derivative, it carries some adverse risks in those patients who have pulmonary/pleural diseases, and likely causes lung fibrosis. Studies have also found some moderate side effects in those who are taking it for Parkinson's disease (NEJM, 2007). Nevertheless, it is not a drug of choice for Parkinsonism, since there are other good medications which are used as first line drugs.
Cabergoline has also been implicated in causing valvular heart disease in one study published in NEJM.
Cabergoline has some (perhaps unknown) interaction with Enzyme: CYP3A4 since it is extensively metabolized by this enzyme in the liver, and has a significant first pass effect. A drug which is a CYP3A4 inhibitor increases the effect of Cabergoline in PD.
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A CYP3A4 inhibitor increased the effect of cabergoline in the treatment of Parkinson's disease
http://onlinelibrary.wiley.com/doi/10.1016/j.clpt.2004.12.204/abstract
A positive outcome:
Cabergoline for levodopa-induced complications in Parkinson's disease
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001518/abstract
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