The “On–Off” Phenomenon in Parkinson’s Disease

Abstract

To determine whether the oscillating clinical response to levodopa in Parkinson's disease (the "on-off" phenomenon) reflects fluctuations in absorption and transport of the drug, we investigated this phenomenon in nine patients with an oscillating motor state. We studied the response to continuous infusion of levodopa and the effects of meals on the plasma levodopa concentrations and on the clinical response during oral and intravenous administration of the drug. Meals reduced peak plasma levodopa concentrations by 29 per cent and delayed absorption by 34 minutes. Bypassing absorption by constant infusion of the drug produced a stable clinical state lasting for 12 hours in all of six patients and for up to 36 hours in some. High-protein meals or oral phenylalanine, leucine, or isoleucine (100 mg per kilogram of body weight) reversed the therapeutic effect of infused levodopa without reducing plasma levodopa concentrations. Glycine and lysine at identical doses had no effect. We conclude that interference with absorption of levodopa by food and by competition between large neutral amino acids and levodopa for transport from plasma to the brain may be partly responsible for the fluctuating clinical response in patients with Parkinson's disease.

Domperidone and levodopa in Parkinson's disease.

“…The change in plasma levodopa concentration with domperidone was unrelated to the Ratio Ratio dose -dp +dp -dp:+dp -dp +dp -dp:+dp Nutt et al (1984) have confirmed and extended previous observations that when levodopa is given with food, there is delayed absorption and a lower peak plasma levodopa concentration that when levodopa is given alone. Likewise, high gastric acidity (RiveraCalimlim et al, 1970) and anticholinergic drugs (Fermaglich & O'Doherty, 1972;Morgan et al, 1975) will delay gastric emptying.…”

Levodopa-Carbidopa Intestinal Gel Infusion Therapy in Advanced Parkinson's Disease: Single Middle Eastern Center Experience

“…LCIG is a very effective treatment modality administered into the proximal jejunum through a PEG tube, where levodopa is absorbed, thus bypassing the stomach and avoiding the risk of levodopa concentration fluctuations associated with erratic or irregular gastric emptying [20]. …”

HELP: Optimizing Treatment of Parkinson’s Disease Patients

“…Levodopa (L-dopa) is the most effective pharmacological agent for pd and remains the primary treatment for symptomatic patients. However, its long-term use is limited by motor complications and drug-induced dyskinesia (Nutt et al, 1984). Unfortunately, the majority of drugs for treating pd, particularly L-dopa, provide pulse stimulation of dopamine release rather than continuous stimulation.…”

“…In later stages of the disease, the fluctuations become less deterministic and totally unpredictable eventually (on-off phenomenon) (Nutt et al, 1984).…”