Motor Efficacy of Subcutaneous DIZ102, Intravenous DIZ101 or Intestinal Levodopa/Carbidopa Infusion.
Parkinson's disease
carbidopa
continuous subcutaneous infusion
levodopa
Journal
Movement disorders clinical practice
ISSN: 2330-1619
Titre abrégé: Mov Disord Clin Pract
Pays: United States
ID NLM: 101630279
Informations de publication
Date de publication:
24 Jun 2024
24 Jun 2024
Historique:
revised:
23
03
2024
received:
19
01
2024
accepted:
13
05
2024
medline:
26
6
2024
pubmed:
26
6
2024
entrez:
26
6
2024
Statut:
aheadofprint
Résumé
It has been suggested that carbidopa at high blood concentrations may counter the therapeutic effect of levodopa in Parkinson's disease by entering the brain and blocking central levodopa conversion to dopamine. We previously demonstrated equivalent plasma levodopa concentration in patients with Parkinson's disease during 16 h of (1) intravenous carbidopa/levodopa (DIZ101) infusion, (2) subcutaneous carbidopa/levodopa (DIZ102) infusion or (3) intestinal carbidopa/levodopa gel infusion. Plasma levels of carbidopa were however approximately four times higher with DIZ101 and DIZ102 than with LCIG, and higher than those usually observed with oral levodopa/carbidopa. To investigate if high carbidopa blood concentrations obtained with parenteral levodopa/carbidopa (ratio 8:1) counter the effect of levodopa on motor symptoms. Eighteen patients with advanced Parkinson's disease were administered DIZ101, DIZ102, and intestinal levodopa/carbidopa gel for 16 h on different days in randomized order. Video recordings of a subset of the motor examination in the Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated by raters blinded for treatment and time. Motor function was also measured using a wrist-worn device monitoring bradykinesia, dyskinesia, and tremor (Parkinson KinetiGraph). There was no tendency for poorer levodopa effect with DIZ101 or DIZ102 as compared to LCIG. Although DIZ101 or DIZ102 causes approximately four times higher plasma carbidopa levels than LCIG, patients responded equally well to all treatments. The results do not indicate that high plasma carbidopa levels hamper the motor efficacy of levodopa.
Sections du résumé
BACKGROUND
BACKGROUND
It has been suggested that carbidopa at high blood concentrations may counter the therapeutic effect of levodopa in Parkinson's disease by entering the brain and blocking central levodopa conversion to dopamine. We previously demonstrated equivalent plasma levodopa concentration in patients with Parkinson's disease during 16 h of (1) intravenous carbidopa/levodopa (DIZ101) infusion, (2) subcutaneous carbidopa/levodopa (DIZ102) infusion or (3) intestinal carbidopa/levodopa gel infusion. Plasma levels of carbidopa were however approximately four times higher with DIZ101 and DIZ102 than with LCIG, and higher than those usually observed with oral levodopa/carbidopa.
OBJECTIVES
OBJECTIVE
To investigate if high carbidopa blood concentrations obtained with parenteral levodopa/carbidopa (ratio 8:1) counter the effect of levodopa on motor symptoms.
METHODS
METHODS
Eighteen patients with advanced Parkinson's disease were administered DIZ101, DIZ102, and intestinal levodopa/carbidopa gel for 16 h on different days in randomized order. Video recordings of a subset of the motor examination in the Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated by raters blinded for treatment and time. Motor function was also measured using a wrist-worn device monitoring bradykinesia, dyskinesia, and tremor (Parkinson KinetiGraph).
RESULTS
RESULTS
There was no tendency for poorer levodopa effect with DIZ101 or DIZ102 as compared to LCIG.
CONCLUSION
CONCLUSIONS
Although DIZ101 or DIZ102 causes approximately four times higher plasma carbidopa levels than LCIG, patients responded equally well to all treatments. The results do not indicate that high plasma carbidopa levels hamper the motor efficacy of levodopa.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Vetenskapsrådet
ID : 2014-07298
Organisme : The Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement
ID : 73220; 77340
Informations de copyright
© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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