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
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 pg.h.ml-1 (mean 7056 pg.h.ml-1) and on day 28 from 3231 to 19043 pg.h.ml-1 (mean 11137 pg.h.ml-1) (dog data).
Distribution
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).
Biotransformation
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).
Elimination
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).