Multicenter study of cabergoline, a long‐acting dopamine receptor agonist, in Parkinson's disease patients with fluctuating responses to levodopa/carbidopa

Abstract

We administered cabergoline, a potent, once-a-day dopamine against, to 61 patients with advanced Parkinson's disease (PD) and response fluctuations--"wearing-off" and "on-off" phenomena. The patients were on stable doses of levodopa/carbidopa. During the first 5 weeks, patients were randomized to allow equal numbers to end titration at each of five daily doses of cabergoline from 0.5 to 2.5 mg. We evaluated the patients using the Unified Parkinson's Disease Rating Scale (UPDRS) and diaries of motor performance. This part of the study was double-blinded. After 5 weeks, the mean Activities of Daily Living (ADL) score on the UPDRS decreased by 22% (p < 0.0001), the mean Motor Score in the "off" period decreased by 14% (p < 0.0001), and the mean Motor Score in the "on" period decreased by 22% (p < 0.0001). The mean percent "off" time decreased by 9.0%. Twenty-three patients (38%) achieved at least a 25% improvement in the combined ADL and motor examination of the UPDRS. Four patients dropped out because of adverse effects. We treated 37 patients, including some patients who had experienced a transient 25% improvement, for an additional 8 weeks in an open manner until they achieved a 25% improvement or reached a maximum of 5 mg/d. The other patients were continued in a double-blind manner on the dose of cabergoline they had achieved at the end of week 5. At the end of 13 weeks, the group of 37 patients achieved additional significant improvements in mean ADL and mean motor scores in the "on" and "off" periods. The percent time "off" decreased by 31%.(ABSTRACT TRUNCATED AT 250 WORDS)

Cabergoline: A Promising Agent for the Treatment of Parkinson's Disease

“…This allowed an 18% reduction of the mean total daily levodopa dose and a 42% reduction in motor "off-time", which decreased from 6.2 to 3.6 hours during CBG therapy. These results support those of previous comparable studies in patients who were experiencing motor fluctuations using levodopa (30,39).…”

Combined effects of cabergoline and L-dopa on parkinsonism in MPTP-treated cynomolgus monkeys

“…In the previous clinical studies (Hutton et al, 1993;Lieberman et al, 1993;Lera et al, 1993;Ahlskog et al, 1994), cabergoline showed the beneficial effects on daily fluctuations in the treatment of advance Parkinson's disease. This drug improved not only "on"-time parkinsonian score but also "off"-time score, and reduced "off"-time period.…”

“…Cabergoline, a DA D2 receptor agonist (Benedetti et al, 1990), exerts long-lasting antiparkinsonian effects in animal experiments (Arai et al, 1995) and reduces "Wearing-off" phenomena found in clinical practice (Hutton et al, 1993;Lieberman et al, 1993;Lera et al, 1993;Ahlskog et al, 1994). The combined effects of treatment with cabergoline and L-dopa may be of therapeutic interest in parkinsonian patients, especially in view of the induction of dopaminergic side effects such as psychosis and dyskinesia.…”

Quantitative determination of cabergoline in human plasma using liquid chromatography combined with tandem mass spectrometry

“…3 A high performance liquid chromatography (HPLC) method with electrochemical detection (quantitation limits 0.2 and 0.3 ng/mL for plasma and urine, respectively) 4 and a radioimmunoassay method (RIA) (quantitation limits 0.08 and 0.15 ng/mL for plasma and urine, respectively) (E. Pianezzola, unpublished results), were initially developed for the assay of unlabelled cabergoline in biological fluids. These methods permitted the evaluation of urinary kinetics of cabergoline, but the determination of plasma levels of the drug was not possible after administration of single doses of cabergoline lower than 1 mg. (Internal report, unpublished results).…”