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Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
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2003 (English)In: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 26, no 3, 156-163 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2003. Vol. 26, no 3, 156-163 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-90200PubMedID: 12782919OAI: oai:DiVA.org:uu-90200DiVA: diva2:162474
Available from: 2003-04-10 Created: 2003-04-10 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Pharmacotherapy for Parkinson's Disease - Observations and Innovations
Open this publication in new window or tab >>Pharmacotherapy for Parkinson's Disease - Observations and Innovations
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pharmacotherapy for Parkinson’s disease (PD) is based on levodopa, the most effective dopaminergic drug. The development of motor complications constitutes the major challenge for new or refined therapies.

To evaluate the impact of levodopa pharmacokinetics on motor function, an observational study in the patients’ home environment was carried out. A high variability in plasma levodopa levels was found in all patients, irrespective of treatment regimen. The impact of levodopa pharmacokinetics was further studied in a crossover trial comparing sustained-release tablets and continuous daytime intestinal infusion. Infusion produced significantly decreased variability in plasma levels of levodopa, resulting in significantly normalised motor function. A permanent system for long-term levodopa infusion has been developed and 28 patients have been followed for 87 patient-years. Motor response was generally preserved during the long-term observation period, implying that there is no development of tolerance to infusion therapy. Levodopa tablets are normally used in multiples of 50 or 100 mg, thus a rough estimate of individual dosage. A new concept for individualising levodopa/carbidopa doses with microtablets of 5/1.25 mg is under development. An electronic drug-dispensing device for administering the microtablets was tested on patients with PD. All were able to handle the dispenser and most were interested in future use of the concept. Self-assessment of symptoms is accurate in PD, but traditional paper diaries are associated with low compliance. A wireless electronic diary was compared with a corresponding paper diary. The time-stamped and thus completely reliable patient compliance was 88% with the electronic diary.

To conclude, pharmacokinetics of levodopa is the major determinant for motor fluctuations in PD. Every effort to individualise dosage and to smooth out the fluctuations in levodopa concentrations should be made, e.g. by means of microtablets or enteral infusion. Electronic patient diaries for real-time data capture are suitable for PD studies.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 99 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1236
Keyword
Neurosciences, Parkinson's disease, levodopa, pharmacokinetics, infusion, drug delivery systems, electronic patient diary, Neurovetenskap
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-3354 (URN)91-554-5571-9 (ISBN)
Public defence
2003-05-06, Grönwallsalen, entrance 70, Uppsala University Hospital, Uppsala, 13:15
Opponent
Supervisors
Available from: 2003-04-10 Created: 2003-04-10 Last updated: 2014-01-29Bibliographically approved

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Nyholm, DagAskmark, HåkanLennernäs, HansAquilonius, Sten-Magnus

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