Dostinex Handbook

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TweetA lot of confusion as to what the intentions and purpose of Dostinex is, have a look at these

Dostinex® Pr
Paladin
Cabergoline
Dopamine Receptor Agonist


Pharmacology

Pharmacodynamic Properties: Cabergoline, the active ingredient in Dostinex, is a dopaminergic ergoline derivative endowed with a potent and long-lasting prolactin-lowering activity. It acts by direct stimulation of the D2-dopamine receptors on pituitary lactotrophs, thus inhibiting prolactin secretion. In rats the compound decreases prolactin secretion at oral doses of 3 to 25 µg/kg, and in vitro at a concentration of 45 pg/mL. In addition, cabergoline exerts a central dopaminergic effect via D2 receptor stimulation at oral doses higher than those effective in lowering serum prolactin levels.

The long-lasting prolactin-lowering effect of cabergoline is probably due to its long persistence in the target organ as suggested by the slow elimination of total radioactivity from the pituitary after a single oral dose in rats (t1/2 of approximately 60 hours).

The pharmacodynamic effects of cabergoline have been studied in healthy volunteers, puerperal women and hyperprolactinemic patients. After a single oral administration of cabergoline (0.3 to 1.5 mg), a significant decrease in serum prolactin levels was observed in each of the populations studied. The effect is prompt (within 3 hours from administration) and persistent (up to 7 to 28 days in healthy volunteers and hyperprolactinemic patients, and up to 14 to 21 days in puerperal women). The prolactin lowering effect is dose-related both in terms of degree of effect and duration of action.

With regard to the endocrine effects of cabergoline not related to the antiprolactinemic effect, available data from humans confirm the experimental findings in animals indicating that the test compound is endowed with a selective action with no effect on basal secretion of other pituitary hormones or cortisol. The pharmacodynamic actions of cabergoline not correlated with the therapeutic effect relate only to blood pressure decrease. The maximal hypotensive effect of a single dose usually occurs during the first 6 hours after drug intake and is dose-dependent both in terms of maximal decrease and frequency.

Pharmacokinetics: The pharmacokinetic and metabolic profiles of cabergoline have been studied in healthy volunteers of both sexes and in female hyperprolactinemic patients. After oral administration of the labeled compound, radioactivity was rapidly absorbed from the gastrointestinal tract as the peak of radioactivity in plasma was between 0.5 and 4 hours. Ten days after administration, about 18% and 72% of the radioactive dose of 14C cabergoline was recovered in the urine and feces, respectively. Unchanged drug in urine accounted for 2 to 3% of the dose.

In urine, the main metabolite identified was 6-allyl-8b-carboxy-ergoline, which accounted for 4 to 6% of the dose. Three additional metabolites were identified in urine, which accounted overall for less than 3% of the dose. The metabolites have been found to be much less potent than cabergoline in inhibiting prolactin secretion in vitro.

The low urinary excretion of unchanged cabergoline has been confirmed also in studies with nonradioactive product. The elimination half-life of cabergoline, estimated from urinary excretion rates, is long (63 to 68 hours in healthy volunteers and 79 to 115 hours in hyperprolactinemic patients as assessed by radioimmunoassay).

The pharmacokinetics of cabergoline were found to be dose-independent in healthy volunteers at doses of 0.5 to 1.5 mg. On the basis of the elimination half-life, steady-state conditions should be achieved after 4 weeks, as confirmed by the mean peak plasma levels of cabergoline obtained after a single dose (37±8 pg/mL) and after a 4-week multiple-dose regimen (101±43 pg/mL). In vitro experiments showed that the drug at concentrations of 0.1 to 10 ng/mL is 41 to 42% bound to plasma proteins.

Food does not appear to affect absorption and disposition of cabergoline.

While renal insufficiency has been shown not to modify cabergoline kinetics, hepatic insufficiency of severe degree (>10 Child Pugh score, maximum score 12) has been shown to be associated with an increase of area under the concentration curve.

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TweetComparison of the effects of cabergoline and bromocriptine on prolactin levels in hyperprolactinemic patients.

Sabuncu T, Arikan E, Tasan E, Hatemi H.

Harran University, Medical Faculty, Department of Endocrinology and Metabolism, Sanliurfa, Turkey.

OBJECTIVE: It is well known that bromocriptine has a suppressive effect on the prolactin release in hyperprolactinemic patients. But it also has some adverse effects. The new, long-acting dopaminergic drug, cabergoline, has been reported to be an effective agent in these patients. However, there are relatively few reports comparing the beneficial and adverse effects of these drugs in the treatment of hyperprolactinemic patients. Therefore, here we studied and compared the efficacy and tolerability of cabergoline with bromocriptine in hyperprolactinemic patients. PATIENTS: Seventeen patients (7 with microprolactinoma, 4 with macroprolactinoma, 6 with idiopathic hyperprolactinemia) were given bromocriptine at a dose of 2.5 mg (or 5 mg for macroprolactinomas) twice daily, and 17 patients (8 with microprolactinoma, 4 with macroprolactinoma, 5 with idiopathic hyperprolactinemia) were given cabergoline at a dose of 0.5 mg twice weekly for 12 weeks. RESULTS: At the end of the study, the prolactin reduction was significantly greater in the cabergoline group than in the bromocriptine group (-93 vs. -87.5 %, respectively, p < 0.05). Normalization of prolactin levels was achieved in 10 of 17 patients (59%) in the bromocriptine group, and in 14 of 17 patients (82%) in the cabergoline group (p = 0.13). Two patients (50%) with macroprolactinoma in the bromocriptine group and three patients (75%) with macroprolactinoma in the cabergoline group demonstrated a normalization of their serum prolactin levels. Adverse events were noted in 53% of bromocriptine patients and in 12% of cabergoline patients (p < 0.01). CONCLUSION: These data indicate that cabergoline is a very effective agent for lowering the prolactin levels in hyperprolactinemic patients and that it appears to offer considerable advantage over bromocriptine in terms of efficacy and tolerability.

Publication Types:
· Clinical Trial
· Randomized Controlled Trial

PMID: 11579944 [PubMed - indexed for MEDLINE]


Ok, this study is basically a comparison between bromocriptine and Cabergoline. Both Ergot derrivatives and Dopamine
Agonists. Bromo being V1.0 and Cabergoline being V2.0 in that regard.
Normally, hyper-prolactinaemic levels are achieved in men/women when they run progestinic based AAS. i.e. Deca, Anadrol amd
Fina.
This is where Cabergoline comes in. It is an extremely good prolactin inhibitor...... 93% prolactin reduction(see study)..
Better than Bromo(87.5%).
High Prolactin levels are also directly linked with male fertility problems. I.e. High prolactin levels = HPTA shut down(in prett much all cases).

Hypogonadism of male prolactinomas: relation to pulsatile secretion of LH.

Saitoh Y, Arita N, Hayakawa T, Onishi T, Koga M, Mori S, Mogami H.

Department of Neurosurgery, Osaka University Medical School, Japan.

In order to investigate whether a hypothalamic disorder cause hypogonadism in male prolactinomas, LH pulsatile secretion was studied in 13 male patients. Serum PRL levels ranged from 186 to 45,000 ng ml-1 before treatment, and all the tumors were macroadenomas. Reduced LH secretion was revealed in 5 of 13 patients, and FSH was reduced in 1 of 13. Serum testosterone (T) levels were lower than the normal limit in all the patients. *** tests in 3 patients showed good responses, but the peak values of T were lower than those of normal men. LH pulsatilities were examined in 5 hyperprolactinemic patients before treatment, in 4 hyperprolactinemic patients after operation, and in 8 normoprolactinemic patients after operation and/or bromocriptine treatment. There was no significant difference of the mean LH values, the frequencies of LH pulses, and amplitudes among the hyperprolactinemic patients before operation (n = 5), the normoprolactinemic patients after operation (n = 8), and normal men (n = 7). From these results, it was evident that the hypothalamus and pituitary function of male prolactinomas were well preserved, in spite of higher serum PRL levels and larger tumor size than those reported in females.

It is suggested that the main cause of hypogonadism in these patients is due to testicular dysfunction resulting from excessive serum PRL.

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TweetThe Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 10 4447-4451
Copyright © 2002 by The Endocrine Society

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CLINICAL CASE SEMINAR

"The Novel Use of Very High Doses of Cabergoline and a Combination of Testosterone and an Aromatase Inhibitor in the Treatment of a Giant Prolactinoma"

Mary P. Gillam, Stewart Middler, Daniel J. Freed and Mark E. Molitch

Division of Endocrinology, Metabolism, and Look! I'm a nut job! Medicine (M.P.G., M.E.M.), Northwestern University, The Feinberg Medical School, Chicago, Illinois 60611; and Cedars-Sinai Medical Center (S.M.), University of California at Los Angeles School of Medicine, Los Angeles, California 90048

Abstract

Most prolactinomas respond rapidly to low doses of dopamine agonists. Occasionally, stepwise increases in doses of these agents are needed to achieve gradual prolactin (PRL) reductions. Approximately 50% of treated men remain hypogonadal, yet testosterone replacement may stimulate hyperprolactinemia.

A 34-yr-old male with a pituitary macroadenoma was found to have a PRL level of 10,362 µg/liter and testosterone level of 3.5 nmol/liter. Eleven months of dopamine agonist therapy at standard doses lowered PRL levels to 299 µg/liter. Subsequent stepwise increases in cabergoline (3 mg daily) further lowered PRL levels to 71 µg/liter, but hypogonadism persisted. Initiation of testosterone replacement resulted in a rise and discontinuation in a fall of PRL levels. Aromatization of exogenous testosterone to estradiol and subsequent estrogen-stimulated PRL release was suspected. Concomitant use of cabergoline with the aromatase inhibitor anastrozole after resuming testosterone replacement resulted in the maintenance of testosterone levels and restoration of normal sexual function, without increasing PRL. Ultimately, further reduction in PRL on this therapy permitted endogenous testosterone production. Thus, novel pharmacological maneuvers may permit successful medical treatment of some patients with invasive macroprolactinomas.