Optimizing Levodopa Pharmacokinetics: Intestinal Infusion Versus Oral Sustained-Release Tablets
- 1 May 2003
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in Clinical Neuropharmacology
- Vol. 26 (3), 156-163
- https://doi.org/10.1097/00002826-200305000-00010
Abstract
Continuous duodenal infusion of carbidopa/levodopa has been shown to control motor fluctuations in advanced Parkinson's disease (PD). The authors compared the pharmacokinetics of levodopa and 3-O-methyldopa in patients with advanced PD after administration of an oral sustained-release levodopa preparation and after continuous intestinal levodopa infusion with a new formulation as a gel suspension. A randomized crossover trial was carried out in 12 patients. Carbidopa/levodopa was administered as an oral sustained-release tablet and by nasoduodenal continuous infusion for 3-week periods for each treatment. Plasma levodopa concentrations and motor performance were evaluated every 30 minutes during 3 test days of each treatment period. The average intraindividual coefficient of variation for the plasma levodopa concentrations after oral therapy was 34% and was significantly lower (14%, p < 0.01) during continuous infusion. Hourly video evaluations showed a significant increase in ON time during infusion and a significant decrease in OFF time and dyskinesia. Continuous intraduodenal delivery of a new carbidopa/levodopa formulation offers a means for markedly improved control of motor fluctuations in late stages of PD.Keywords
This publication has 22 references indexed in Scilit:
- Levodopa Pharmacokinetics and Motor Performance During Activities of Daily Living in Patients With Parkinson's Disease on Individual Drug CombinationsClinical Neuropharmacology, 2002
- Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnoverAnnals of Neurology, 2001
- Continuous dopamine-receptor stimulation in advanced Parkinson's diseaseTrends in Neurosciences, 2000
- The significance of continuous dopaminergic stimulation in the treatment of Parkinson's disease.Drugs, 1998
- Regional Intestinal Permeability in Rats of Compounds with Different Physicochemical Properties and Transport MechanismsJournal of Pharmacy and Pharmacology, 1997
- Levodopa‐induced changes in synaptic dopamine in patients with Parkinson's disease as measured by [ 11 C]raclopride displacement and PETNeurology, 1996
- Effect of peripheral catechol‐O‐methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patientsNeurology, 1994
- The effect of L‐leucine on the absorption of levodopa, studied by regional jejunal perfusion in man.British Journal of Clinical Pharmacology, 1993
- Cerebral uptake and utilization of therapeutic [β-11C]-L-DOPA in Parkinson's disease measured by positron emission tomography. Relations to motor responseActa Neurologica Scandinavica, 1992
- Erratic gastric emptying of levodopa may cause “random” fluctuations of parkinsonian mobilityNeurology, 1988