Fluctuations in motor performance are the major problems in chronic management of
Parkinson's disease. Most of these fluctuations reflect the decline of
levodopa availability. As a consequence,
levodopa dosage might be increased and the interdose interval progressively shortened. The postsynaptic
dopamine receptors at this point are exposed to a nonphysiologic shift in
dopamine level, which may induce changes at the receptor site and contribute to the appearance of "on-off" phenomena and
dyskinesias. We compared a group of 18 patients treated for 60 consecutive months with continuous subcutaneous
lisuride infusion with a group of 20 patients treated with conventional oral
levodopa treatment. The clinical evaluations performed during the study showed in the
lisuride group only a worsening of
dyskinesias, whereas the other symptoms remained unchanged. In the other group the evaluation scores showed a significant worsening of all long-term treatment complications. The slow-release preparations of
levodopa may ensure a more continuous dopaminergic stimulation than standard formulations. However, the use of these compounds is difficult in severely fluctuating patients because the lack of a plasma peak level usually leads to a very long delay before patients turn "on." We studied the pharmacokinetic and clinical effects of the two slow-release preparations of
levodopa [
Madopar HBS and
Sinemet controlled-release (CR)] and a combination of
Sinemet CR plus standard
Sinemet in 13 fluctuating parkinsonian patients. The results of this study show that the combination of standard
Sinemet and
Sinemet CR ensures a more prolonged clinical effect with a very short latency to the "on" phase.