Levodopa In Parkinsonian Patients Research Articles

Influence of meal ingestion time on pharmacokinetics of orally administered levodopa in parkinsonian patients.

The influence of meal ingestion time on rate and extent of oral levodopa absorption was evaluated in a group of 17 patients, after administration of their usual second daily dose of levodopa plus carbidopa (Sinemet 10:1) or benserazide (Madopar 4:1). Standard meals were consumed by the patients after they had fasted 15-17 h, on one occasion 30 min before ingestion of the levodopa "study dose" and, at another time, 2 h after ingestion of the same dose. This study dose, ranging from 50 to 250 mg levodopa, was given to the patients at 11 a.m., 4 h after their first morning dose. Time to peak plasma levodopa concentration increased threefold (from 45 +/- 23 to 134 +/- 76 min, p less than 0.001), when levodopa was administered after meals. Area under the 6-h plasma concentration-time curve for levodopa was decreased in 10 subjects, unchanged in three and higher in four after ingestion of meals, the latter finding probably resulting from an erratic absorption even at fasting. On the whole, levodopa absorption proved significantly lower (p less than 0.01), on the average 15%. Similarly, peak plasma levodopa concentrations were lower in 12 patients, unchanged in two, and higher in three, with an overall significant decrease (p less than 0.001) of 30% on the average. The data confirm the importance of meal ingestion time in relation to levodopa dose as a determinant of drug absorption.

A quantitative study of the electroencephalographic response to levodopa treatment in parkinsonian patients.

A quantitative EEG study was done in order to confirm previous impressions that there is a significant EEG response to levodopa in parkinsonian patients, and in order to trace the existence of dopaminergic mechanisms in the generation of the human EEG. EEGs of twenty-five parkinsonian patients were recorded both before and during levodopa treatment, two to four weeks apart, when levodopa doses reached maintenance levels of 3-5g/d. Derivations from F7-T3, F8-T4, T5-O1, and T6-O2 were recorded and digitally processed into power density spectra. These spectra were analyzed for levodopa effects in a full factorial repeated measures multiple analysis of variance (MANOVA). A significant effect of levodopa treatment on the EEG was found, and localized to the left occipital lobe. This effect manifested as an increase in power in all the EEG frequency bands. These findings are compatible with multiband synchronization of the EEG generating processes, attributable to dopaminergic mechanisms.

Treatment of Parkinson's disease: problems with a progressing disease.

Long-term follow-up of parkinsonian patients has shown that although levodopa treatment significantly improves the parkinsonian symptoms and the quality of life of parkinsonian patients for several years, various distressing difficulties arise during chronic levodopa treatment, such as the loss of benefit, dyskinesias, on-off phenomena, postural instability and dementia. Clinical, neuropsychological, mortality and post-mortem brain studies indicate that levodopa as a replacement therapy does not modify the progression of the underlying pathology and the natural course of the disease. It seems that levodopa has only a limited period of optimal usefulness in the treatment of Parkinson's disease. However, at present there is no better or more potent therapeutic agent available than levodopa and it is still the primary treatment of Parkinson's disease. It would be reasonable not to begin levodopa treatment in patients with mild symptoms but to withhold levodopa until the severity of symptoms really makes its use necessary. Thus it is possible to get the maximal long functional benefit. Post-mortem brain studies have shown that in Parkinson's disease there is not only a progressive loss of dopaminergic substantia nigra neurons but there are also significant changes in the striatal dopamine receptors. In some patients a denervation supersensitivity seems to develop and in some others a loss of dopamine receptors in the striatum. However, in advanced parkinsonian patients with a deteriorating response to levodopa, there seem to be still enough dopamine receptors in the striatum for drugs stimulating the dopamine receptors directly to improve the parkinsonian disability. Indeed, recent evidence indicates that dopaminergic agonists, such as bromocriptine, seem to be a significant and valuable adjuvant therapy to levodopa in parkinsonian patients with a deteriorating response and/or the on-off phenomena. Although bromocriptine is not completely satisfactory, it is a significant opening to a new mode of treatment. In the future it will be very important to develop more potent and selective dopaminergic agonists affecting only those striatal receptors which are mainly responsible for the parkinsonian symptoms. Then a better therapeutic response is likely to occur and many central side effects can be avoided. Current difficulties in the management of Parkinson's disease greatly depend on the fact that we are dealing with a symptomatic therapy. It is hoped that future research will soon lead to a discovery of the primary cause and consequently to a causal therapy of Parkinson's disease.

Effects of levodopa in Parkinsonian patients with dementia.

Effects of levodopa in Parkinsonian patients with dementia.