Effectiveness of Continuous Dopaminergic Therapies in Parkinson's Disease: A Review of L-DOPA Pharmacokinetics/Pharmacodynamics. - Université de Lille Accéder directement au contenu
Article Dans Une Revue (Article De Synthèse) Journal of Parkinson's disease Année : 2024

Effectiveness of Continuous Dopaminergic Therapies in Parkinson's Disease: A Review of L-DOPA Pharmacokinetics/Pharmacodynamics.

Résumé

Background: Parkinson’s disease (PD) is characterized by striatal dopamine deficiency. Since dopamine cannot cross the digestive and blood-brain barriers, its precursor, levodopa (L-DOPA), remains the mainstay of treatment. However, the significant pharmacokinetic (Pk) and pharmacodynamic (Pd) limitations of L-DOPA, combined with the severity of PD, may trigger motor and non-motor complications, for which continuous dopaminergic delivery therapies have been developed. Objective: The aim of this study was to review the literature on the Pk/Pd limitations of L-DOPA and how current treatments of continuous dopaminergic administration ameliorate these problems, in order to identify the need for new therapeutic avenues. Methods: A comprehensive literature search was carried out using PubMed and 75 articles were initially extracted. Following independent screening by two reviewers and consideration of eligibility, 10 articles were chosen for further analysis. Information concerning the Pk/Pd of L-DOPA was classified for each article. Results: Pk/Pd problems notably include: (i) restricted digestive and cerebral absorption; (ii) unnecessary peripheral distribution; (iii) short half-life; (iv) age- and PD-induced decline of central aromatic L-amino acid decarboxylase; (v) misdistribution in many cells; and (vii) pulsatile stimulation of dopaminergic receptors. Current treatments only slightly ameliorate some of these problems. Conclusions: Many Pk/Pd constraints are not resolved by existing continuous dopaminergic delivery therapies. This highlights the significant gap between these treatments and the ideal of continuous dopaminergic stimulation.
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hal-04621596 , version 1 (24-06-2024)

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Alexandre Demailly, Caroline Moreau, David Devos. Effectiveness of Continuous Dopaminergic Therapies in Parkinson's Disease: A Review of L-DOPA Pharmacokinetics/Pharmacodynamics.. Journal of Parkinson's disease, 2024, Journal of Parkinson's disease, Online ahead of print. ⟨10.3233/JPD-230372⟩. ⟨hal-04621596⟩

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