Bromocriptine was approved in the United States in 1978. This ergot alkaloid is a partial D2 agonist and a mild adrenergic agonist. It also has mild D1 and 5-HT- antagonist properties (Table 1). When taken orally, bromocriptine is rapidly absorbed and 90% degraded through first-pass hepatic metabolism. Peak drug levels are achieved in 70 to 100 minutes, and it has a half-life of three to eight hours. Less than 5% of the drug is excreted into the urine, and it is highly protein bound (Table 2). Bromocrip-tine is formulated into 2.5 mg-scored tablets and 5 mg capsules (1). Bromocriptine is initiated at 1.25 mg/d and is generally increased to 20mg/d in three divided doses over the course of seven weeks; however, some patients may require dosages higher than 60 mg/d (Table 3) (15).

Although the side effects of all dopamine agonists are similar, only the ergot-derived compounds have been associated with retroperitoneal fibrosis—a rare but serious condition associated with severe pulmonary and renal complications (16). Erythromelalgia, a painful reddish discoloration of the anterior shin, may also be more prevalent in patients taking ergoline dopamine agonists. The side effects of nausea, vomiting, sleepiness, orthostatic hypotension, and hallucinations are common to all dopamine agonists and in pivotal trials these side effects were 8% to 12% more common with bromocriptine than with placebo (17) (Table 2).

Bromocriptine has been investigated in de novo and levodopa-treated PD patients (18-22). A systematic review of all randomized, controlled trials of bromocriptine monotherapy compared with levodopa monotherapy in PD found that methodological factors or lack of control populations have led to a lack of evidence to guide clinical decisions (19-21). From 1974 to 1999, six studies randomizing more than 850 PD patients to bromocriptine or levodopa were reported, but only

TABLE 3 Agonist Titration Schedule






Week 1

1.25 mg qd

0.05 mg qd

0.125 mg tid

0.25 mg tid

Week 2

1.25 mg bid

0.05 mg tid

0.25 mg tid

0.50 mg tid

Week 3

1.25 mg tid

0.10mg tid

0.50 mg tid

0.75 mg tid

Week 4

2.50 mg tid

0.15mg tid

0.75 mg tid

1.00mg tid

Week 5

3.75 mg tid

0.25 mg tid

1.00 mg tid

1.50mg tid

Week 6

5.00 mg tid

0.50 mg tid

2.00 mg tid

Week 7

5.00 mg qid

0.75 mg tid

2.50 mg tid

Week 8

1.00mg tid

3.00 mg tid

Maximum dosage

15.0 mg qid

2.00 mg qid

1.5 mg tid

8.00 mg tid

Source: From Ref. 15.

Source: From Ref. 15.

two trials used a double-blind design (19-21). These studies indicated a reduced frequency of dyskinesia and a trend toward less wearing off with bromocriptine. However, the larger number of dropouts in the bromocriptine group leaves these data subject to varied interpretations. In the treatment of early PD, bromocriptine may be beneficial in delaying motor complications and dyskinesia with comparable effects on impairment and disability in patients who tolerate the drug.

Numerous studies have demonstrated the benefits of bromocriptine in advanced PD. A double-blind, placebo-controlled, multicenter trial of bromocriptine in patients with motor fluctuations reported a 14% improvement in UPDRS activities of daily living (ADL), a 23.8% improvement in UPDRS motor scores and a 29.7% reduction in off time after nine months, with a mean daily dosage of 22.8 mg of bromocriptine (22).

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