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Pharmacological particulars
ATCvet code: QG02CB03
Pharmacodynamic properties
Cabergoline is a prolactin inhibitor belonging to the ergoline derivative group which acts by dopamine agonist activity.
The pharmacodynamics of cabergoline have been investigated in various in-vitro and in-vivo systems. The most significant findings can be summarised as follows:
- Cabergoline is a potent inhibitor of prolactin secretion by the pituitary, and as a consequence inhibits prolactin secretion dependent processes such as lactation. Peak prolactin inhibition is reached at 4-8 hours and persists for several days, depending on the dose. The antiprolactin effect of cabergoline is longer lasting than that of metergoline, bromocriptine and pergolide.
- The mechanism of action of cabergoline is via direct interaction with the dopamine receptor on pituitary lactotroph cells; this interaction is a persistent effect.
- Apart from its effect on prolactin dependent processes, cabergoline does not have any other significant endocrine effects.
- In the Central Nervous System, cabergoline has dopamine agonist activity, acting via the D-2 dopaminergic receptors.
- Cabergoline has some affinity for noradrenergic receptors, but does not affect noradrenaline or serotonin metabolism.
- As for other ergoline derivatives, cabergoline has emetic effects (equivalent in potency to those of pergolide and bromocriptine).
- Given parenterally, or at high doses orally, cabergoline causes a reduction in blood pressure.
Pharmacokinetic particulars
Pharmacokinetic studies were performed in both rats and dogs. The studies in rats were undertaken with radiolabeled cabergoline, by oral or intravenous administration, at a dose of 0.5 mg/kg bodyweight. The studies in dogs were performed with a daily dose of 80 µg/kg bodyweight (the dogs were treated for 30 days; pharmacokinetic assessments made on day 1 and 28). The source of the information given below is specified (rat data or dog data).
Absorption after oral administration is nearly complete (rat data).
Tmax = 1 hour on day 1 and 0.5-2 hours (mean 75 minutes) on day 28 (dog data);
Cmax ranged from 1140 to 3155 pg/ml (mean 2147 pg/ml) on day 1 and from 455 to 4217 pg/ml (mean 2336 pg/ml) on day 28 (dog data);
AUC (0-24 h) on day 1 ranged from 3896 to 10216 (mean 7056 and on day 28 from 3231 to 19043 (mean 11137 (dog data).
In terms of tissue to plasma concentration ratio (AUC), the tissue uptake was very high for liver, pituitary, adrenals, spleen, kidneys, lung (260-100), followed by ovaries, uterus, heart (50-30). In the brain the levels were of the same order of magnitude as in plasma (rat data).
Assessment of plasma metabolites: consistent amounts of four metabolites (FCE 21589, FCE 21904 and two unknown) were detected in plasma in addition to unchanged cabergoline which accounted for about 26% of plasma radioactivity from 2 to 48 hours after oral administration. Large amounts of metabolites were already present at the first sampling times (0.5 and 1.0 hours) suggesting a rapid biotransformation of cabergoline even of presystemic origin (rat data);
Assessment of excreted metabolites in the urine excreted up to 24 hours after oral and intravenous dosing: about 25% of the excreted radioactivity was represented by unchanged drug, about 50% by the metabolite 6-ADL (FCE 21589) and the remaining 25% by other currently unknown metabolites (rat data).
Plasma half life in dogs: t½ on day 1 ~ 19 hours; t½ on day 28 ~ 10 hours (dog data);
Tissue half life in rats: The rate of elimination from most tissues (t½ ~ 17 hours) except for the pituitary where elimination was particularly slow (t½ ~ 60 hours) (rat data).
Excretion route in rats: The main route of excretion was faecal; not more than 10% of the dose was recovered in the urine (rat data).