Pergolide: multiple-dose pharmacokinetics in patients with mild to moderate Parkinson disease.

Abstract:

:The primary objective of this study was to describe the pharmacokinetics of oral pergolide in patients with mild to moderate Parkinson disease using a new high-performance liquid chromatography-tandem mass spectrometry assay. A secondary objective was to investigate the relationship between plasma concentrations and efficacy. Fourteen patients with a diagnosis of Parkinson disease completed this multicenter, open-label, dose-escalating study. Pergolide was administered for 58 days, using increasing daily doses from 0.05 mg daily up to 1 mg three times daily and then tapering the dose. The steady-state pharmacokinetic profile and motor score were determined at dose levels of 0.25, 0.5, and 1 mg three times a day and during elimination after the last dose. Pergolide was absorbed with a median time to maximum concentration of 2 to 3 hours across the dose range. Systemic exposure appeared to increase proportionally with dose over the range of 0.25 to 1 mg three times daily within a patient, but there was a large variability in exposures between patients (interpatient coefficients of variation were 56.4% for the area under the curve). Pergolide was widely distributed (volume of distribution, approximately 14,000 L) and was eliminated with a mean half-life of 21 hours. Motor scores improved as both peak plasma pergolide concentrations and exposure increased. No unexpected safety concerns were identified. Pergolide is absorbed relatively quickly into the systemic circulation, has a large apparent volume of distribution, and has a relatively long half-life (mean, 21 hours). This prolonged half-life is of particular interest, given the current hypothesis that more continuous dopaminergic receptor stimulation may reduce motor complications in patients with Parkinson disease.

journal_name

Clin Neuropharmacol

authors

Thalamas C,Rajman I,Kulisevsky J,Lledó A,Mackie AE,Blin O,Gillespie TA,Seger M,Rascol O

doi

10.1097/01.wnf.0000168581.97083.9c

keywords:

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

120-5

issue

3

eissn

0362-5664

issn

1537-162X

pii

00002826-200505000-00005

journal_volume

28

pub_type

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