Cabergoline in the treatment of early parkinson's disease

Abstract

Cabergoline is a potent D2 receptor agonist with a half-life of 65 hours that may provide continuous dopaminergic stimulation administered once daily. In this study, we randomized de novo Parkinson's disease (PD) patients to treatment with increasing doses of cabergoline (0.25 to 4 mg/d) or levodopa (100 to 600 mg/d) up to the optimal or maximum tolerated dose. Decreases of > 30% in motor disability (Unified Parkinson's Disease Rating Scale Factor III) versus baseline were considered indicative of clinical improvement. If 30% improvement was not achieved, levodopa/ carbidopa could be added on an open basis. Of the 208 patients entered in the cabergoline group, 175 remained in the study for 1 year at a mean dose of 2.8 mg/d; in the levodopa group, 176 of the 205 patients entered were still on study after 1 year at a mean dose of 468 mg/d. The proportion of patients requiring additional levodopa/carbidopa increased in the cabergoline group from 18% at 6 months to 38% at 1 year versus 10% (p = 0.05) at 6 months and 18% (p < 0.01) at 1 year in the levodopa group. The proportion of patients showing clinical improvement did not differ significantly between the two groups, or between the subgroups on monotherapy, at any endpoint. Irrespective of levodopa/carbidopa addition, 81% of patients in the cabergoline group and 87% of patients in the levodopa group were clinically improved at 1 year (p = 0.189); the corresponding figures for the subgroup on monotherapy were 79% in the cabergoline-treated patients and 86% in the levodopa-treated patients (p = 0.199). The mean difference versus baseline in Unified Parkinson's Disease Rating Scale Factor III scores in patients who remained on monotherapy up to 1 year was 12.6 (95% confidence interval [CI]: 10.8, 14.3) in the cabergoline group and 16.4 (95% CI: 14.8, 18.0) in the levodopa group. Adverse events occurred in 76% of patients on cabergoline and in 66% of patients on levodopa. The severity profile for reported events was similar for the two agents. The results of this study indicate that cabergoline treatment for up to 1 year is only marginally less effective than levodopa in the proportion of patients who can be treated in monotherapy. More than 60% of de novo PD patients could be managed on cabergoline alone up to 1 year. In the patients in whom levodopa/carbidopa was needed, the combination therapy provided efficacy similar to that obtained with levodopa alone, with a relevant sparing of levodopa.

Cabergoline Induced Supraventricular Tachycardia with QT Prolongation

“…3 Cabergoline is absorbed from the gastrointestinal tract within 0.5 to 4 h 2 and has an average elimination half-life of 65 h that may provide continuous dopaminergic stimulation when administered once daily. 8 Although the patient had delayed onset of symptoms, the long elimination half-life of cabergoline may contribute to its prolonged duration of action and persistence of symptoms even after drug withdrawal, as observed in our patient. The duration of QT interval is the major determinant of the risk of drug-induced TdP.…”

Practice parameter: Initiation of treatment for Parkinson’s disease: An evidence-based review [RETIRED]

“…Levodopa appeared to be better than cabergoline for improvement in both part II (ADL) and part III (motor) of the UPDRS, 30 but the publication does not report a statistical comparison of these data. After 4 years in the clinical trial, levodopa subjects still showed an average of 30% improvement in motor disability (part III), while patients treated with cabergoline showed a 22 to 23% improvement.…”

“…Adverse events were higher in the cabergoline group (75.8%) versus levodopa (65.7%), with nausea being the most common in both. 30 In the study of ropinirole versus levodopa, 6 the primary endpoint was dyskinesias rather than other types of motor complications. The absolute risk reduction for dyskinesias after 5 years of treatment was 26% for the ropinirole group (monotherapy or with the later addition of levodopa adjunctive therapy).…”

Spectrophotometric Determination of Dopaminergic Drugs Used for Parkinson's Disease, Cabergoline and Ropinirole, in Pharmaceutical Preparations

“…2,3) A few high-performance liquid chromatographic (HPLC) methods have been developed for the determination of CAB in plasma using electrochemical detection, 4) tandem mass spectrophotometry (TMS) [5][6][7] or triple-quadrupole mass spectrometry. 8) ROP, 4-[2-(dipropylamino)ethyl]-l,3-dihydro-2H-indol-2-one hydrochloride, is a specific D2 and D3 receptor non-ergoline dopamine agonist that is probably equally effective as L-dopa in mild, early Parkinson's disease.…”