Everything that I have read/felt lead me to believe that this is caused by fluctuation which gets more as the effective response to dose becomes shorter etc, I believe better management would help reduce this. (This is where patient led information could really start to make a difference.) And I do too believe that it is peak dose that gives the toxic feeling and then the later feeling of being 'better' which then gives way to a return of symptoms. We would get an easier ride and less side effects if this aspect of levodopa therapy was really tackled i.e. we didnt have to search for this information ourselves but were taught how to manage our drugs in the same way that diabetics are taught to manage insulin. Here is an abstract that seems to confirm this:

http://content.nejm.org/cgi/content/...ract/310/8/483

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.