Cabergoline: Long-Acting Oral Treatment of Hyperprolactinemic Disorders

Abstract

Cabergoline, a new orally active dopaminergic drug with an extremely long-lasting PRL-lowering effect, was given to 48 hyperprolactinemic women for 3-18 months (median, 8 months) at doses varying between 0.2-3 mg/week administered one to three times weekly. Serum PRL levels declined to normal in 41 women, 30 of whom received 0.2-1 mg cabergoline once weekly, 8 received 0.2-0.5 mg twice weekly, and 3 received 0.4-0.6 mg 3 times weekly. Five women had slightly supranormal serum PRL levels while receiving 0.3-0.6 mg once weekly, but the dose was not increased because the lower dose had produced the desired clinical benefit. Two women had 50% reductions in their serum PRL levels, but remained hyperprolactinemic while receiving 2-3 mg cabergoline weekly. Among 30 amenorrheic women, 28 had resumption of menses, the exceptions being 2 hypopituitary women, presumptive evidence of ovulation was available in 21. Marked tumor shrinkage occurred after 3-month treatment in 5 of the 6 women who had macroprolactinomas. Only 4 women had side-effects during the first weeks of treatment, and these vanished despite continued cabergoline administration at the same or reduced, but still effective, doses. In a short term, double blind study, cabergoline at 3 different schedules (0.4 mg twice weekly, 0.2 mg 4 times weekly, and 0.4 mg 3 times weekly for 3 weeks, followed by 0.4 mg twice weekly) or placebo was given to a total of 24 hyperprolactinemic women (6 in each subgroup) for 8 weeks, with weekly evaluation of serum PRL levels and side-effects. All 3 cabergoline schedules, but not placebo, induced significant reductions in serum PRL concentrations during the 8-week treatment period. Mild transient side-effects occurred in 7 drug-treated patients (nausea in 5; dizziness in 3). We conclude that cabergoline is effective treatment for hyperprolactinemia. Its efficacy, tolerability, and long duration of action may make it the drug of choice for patients with hyperprolactinemia.

In vivo Effect of Cabergoline, a Dopamine Agonist, on Estrogen-Induced Rat Pituitary Tumors.

“…Those authors found that a single oral dose of CG induced a marked fall in serum PRL level that persisted for 72 h in rats [10], and for 7 days in humans [15].…”

“…Thus, CG induced a prolonged lowering of PRL and had a good antitumor effect on rat pituitary tumors induced by estrogen. Correspondence to: Dr. Kuniki EGUCHI, Department of Neurosurgery, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan also exhibits a potent PRL-lowering effect and an antitumor effect in animals and humans [10][11][12][13][14][15][16][17]. Its mechanism of action in reducing tumor size has never been reported.…”

“…also exhibits a potent PRL-lowering effect and an antitumor effect in animals and humans [10][11][12][13][14][15][16][17]. Its mechanism of action in reducing tumor size has never been reported.…”

Comparison among Different Dopamine-Agonists of New Formulation in the Clinical Management of Macroprolactinomas

“…These reactions are likely due to the rapid absorption of the drug which is administered two or three times a day, thus causing high blood levels. In order to improve the tolerance, several drugs with differ ent molecular structure or half-life have been tested: some are ergot derivatives with half-lives similar to (lisuride, pergolide, mesulergine) [6,7] or longer than BRC (caber goline) [8], others represent new formulations of BRC with different pharmacokinetics providing a long-lasting effect in monthly i.m. injection (BRC-LAR) [9][10][11][12][13] or in single daily oral administration (BRC-SRO) [13][14][15], Fi nally, there is a non-ergot derivative which selectively binds dopamine D?…”

Usefulness of CV 205-502 in a Case of Allergy to Ergot-Derived Drugs

“…In fact, BRC and lisuride are ergot-derived drugs while CV 205-502 is a nonergotderived drug [6,7], The poor tolerance to the conven tional therapy with BRC has caused the introduction in clinical practice of other drugs, i.e. lisuride, pergolide, lergotrile, metergoline, cabergoline [8,9] and new formula tions of BRC characterized by slow release, such as the injectable and repeatable form (Parlodel LAR) and the slow oral release form (Parlodel SRO) [10][11][12], All these drugs are ergot-derived dopamine agonists. They are effective in the medical treatment of hyperprolactinemic states and represent a good alternative in patients resis tant or intolerant to BRC.…”