CLINICAL PHARMACOLOGY
Bromocriptine mesylate is a dopamine receptor agonist, which activates postsynaptic dopamine receptors. The dopaminergic neurons in the tuberoinfundibular process modulate the secretion of prolactin from the anterior pituitary by secreting a prolactin inhibitory factor (thought to be dopamine); in the corpus striatum the dopaminergic neurons are involved in the control of motor function. Clinically, bromocriptine mesylate significantly reduces plasma levels of prolactin in patients with physiologically elevated prolactin as well as in patients with hyperprolactinemia. The inhibition of physiological lactation as well as galactorrhea in pathological hyperprolactine-mic states is obtained at dose levels that do not affect secretion of other tropic hormones from the anterior pituitary. Experiments have demonstrated that bromocriptine induces long lasting stereotyped behavior in rodents and turning behavior in rats having unilateral lesions in the substantia nigra. These actions, characteristic of those produced by dopamine, are inhibited by dopamine antagonists and suggest a direct action of bromocriptine on striataldopamine receptors. Bromocriptine mesylate is a nonhormonal, nonestrogenic agent that inhibits the secretion of prolactin in humans, with little or no effect on other pituitary hormones, except in patients with acromegaly, where it lowers elevated blood levels of growth hormone in the majority of patients.
In about 75% of cases of amenorrhea and galactorrhea, bromocriptine mesylate therapy suppresses the galactorrhea completely, or almost completely, and reinitiates normal ovulatory menstrual cycles.
Menses are usually reinitiated prior to complete suppression of galactorrhea; the time for this on average is 6 to 8 weeks. However, some patients respond within a few days, and others may take up to 8 months.
Galactorrhea may take longer to control depending on the degree of stimulation of the mammary tissue prior to therapy. At least a 75% reduction in secretion is usually observed after 8 to 12 weeks. Some patients may fail to respond even after 12 months of therapy.
In many acromegalic patients, bromocriptine mesylate produces a prompt and sustained reduction in circulating levels of serum growth hormone.
Bromocriptine mesylate produces its therapeutic effect in the treatment of Parkinson's disease, a clinical condition characterized by a progressive deficiency in dopamine synthesis in the substantia nigra, by directly stimulating the dopamine receptors in the corpus striatum. In contrast, levodopa exerts its therapeutic effect only after conversion to dopamine by the neurons of the substantia nigra, which are known to be numerically diminished in this patient population.
Pharmacokinetics
The pharmacokinetics and metabolism of bromocriptine in human subjects were studied with the help of radioactively labeled drug. Twenty-eight percent of an oral dose was absorbed from the gastrointestinal tract. The blood levels following a 2.5 mg dose were in the range of 2 to 3 ng equivalents/mL. Plasma levels were in the range of 4 to 6 ng equivalents/mL indicating that the red blood cells did not contain appreciable amounts of drug and/or metabolites. In- vitro experiments showed that the drug was 90% to 96% bound to serum albumin.
Bromocriptine was completely metabolized prior to excretion. The major route of excretion of absorbed drug was via the bile. Only 2.5% to 5.5% of the dose was excreted in the urine. Almost all (84.6%) of the administered dose was excreted in the feces in 120 hours.
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