Peripheral and central pharmacokinetics of apomorphine and its effect on dopamine metabolism in humans.

Details

Serval ID
serval:BIB_0FD30B941F6F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Peripheral and central pharmacokinetics of apomorphine and its effect on dopamine metabolism in humans.
Journal
Movement Disorders
Author(s)
Przedborski S., Levivier M., Raftopoulos C., Naini A.B., Hildebrand J.
ISSN
0885-3185 (Print)
ISSN-L
0885-3185
Publication state
Published
Issued date
1995
Peer-reviewed
Oui
Volume
10
Number
1
Pages
28-36
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Apomorphine is a dopamine receptor agonist increasingly used in the treatment of Parkinson's disease (PD). In the present study, we examined the plasma and ventricular cerebrospinal fluid (CSF) pharmacokinetics of apomorphine as well as its effects on dopamine metabolism in six patients (one woman and five men, mean age 79.5 years) without evidence of PD who underwent 48-h intracranial pressure monitoring for suspected normal pressure hydrocephalus. Maximal plasma apomorphine concentration (25.04 ng/ml) is found 20 min after subcutaneous injection (50 micrograms/kg), and the mean area under the curve is 1,439.37 ng/ml for 120 min. In contrast to plasma values, the maximal ventricular CSF apomorphine concentration (1.08 ng/ml) is found 30 min after injection and the mean area under that curve is 7% of that of plasma (96.69 ng/ml for 120 min). Apomorphine administration causes a significant reduction in ventricular CSF concentrations of dopamine and of its major metabolites sulfoconjugated dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA). This effect starts 10 min after the injection of apomorphine, is maximal after 30 min (free dopamine, -30%; sulfoconjugated dopamine, -28%; HVA, -21%; DOPAC, -31%) and is still present, although to a lesser extent (-5 to -10%), 120 min after the injection of apomorphine. This study shows that in humans a dose of apomorphine commonly used in PD causes significant inhibition of dopamine metabolism lasting > 120 min. In addition to their symptomatic effects, dopamine agonists such as apomorphine may play a role in preventing or slowing the neurodegeneration in PD by autoreceptor-mediated inhibition of dopamine metabolism.
Keywords
3,4-Dihydroxyphenylacetic Acid/cerebrospinal fluid, Aged, Apomorphine/blood, Apomorphine/cerebrospinal fluid, Chromatography, High Pressure Liquid, Dopamine/cerebrospinal fluid, Dopamine/metabolism, Female, Homovanillic Acid/cerebrospinal fluid, Humans, Hydrolysis, Male, Middle Aged
Pubmed
Web of science
Create date
20/01/2008 17:35
Last modification date
20/08/2019 12:36
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