Bromocriptine: A Sympatholytic, D2-dopamine Agonist for the Treatment of Type 2 Diabetes

Ralph A. DeFronzo, MD

Disclosures

Diabetes Care. 2011;34(4):789-794. 

In This Article

Pharmacokinetics and Dose

Following ingestion, Cycloset (bromocriptine mesylate) tablets are rapidly dissolved and absorbed within 30 min.[29] When ingested on an empty stomach, the maximum plasma concentration is reached within 60 min. Absorption is delayed by food and peak plasma levels are achieved at ~120 min in the fed state. There is extensive hepatic first-pass extraction and metabolism, and only 5–10% of the ingested dose reaches the systemic circulation.[33–35] Ninety-eight percent of ingested bromocriptine is excreted via the biliary route with an elimination half-life of ~6 h. Within the liver, bromocriptine is extensively metabolized by the cytochrome P450 system, specifically CYP3A4. There are some 20–30 metabolites, but their biologic activity is largely unknown.

Cycloset differs from traditional bromocriptine formulations, such as Parlodel, in its quick release that provides peak concentrations within 60 min. There is no AB-rated equivalent for Cycloset. Cycloset comes as 0.8 mg tablets. The starting dose is 0.8–1.6 mg/day and can be titrated to a maximum of 4.6 mg/day. Cycloset is administered as a once daily dose within 2 h of awaking. Type 2 diabetic individuals are believed to have an early morning dip in dopaminergic tone, which leads to increased sympathetic activity.[25] In vertebrate species circadian plasma prolactin levels closely parallel changes in hypothalamic levels of dopamine and insulin sensitivity (rev. in[7] and[32]). In lean, normal glucose-tolerant insulin-sensitive humans, plasma prolactin concentrations peak at night during sleep. In contrast, obese insulin-resistant individuals have elevated (twofold) day time plasma prolactin levels,[29] consistent with reduced dopaminergic tone.[36] Administration of Cycloset within 2 h of awakening reduces the elevated prolactin levels[29,37,38] and is thought to restore dopaminergic activity, thereby reducing postprandial plasma glucose, triglyceride, and FFA concentrations without increasing plasma insulin levels (see subsequent discussion).

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