I have been searching for studies to substantiate my opinion on levodopa and its negative perception here (at least in the states). Yes, it is still addictive and causes unwanted movements, but it is not inherent to the drug itself but to the oral delivery route. All I ever see written is how levodopa is only efficacious for five years and that it fails due to progression. Where are the studies supporting this?

We each metabolize levodopa differently depending on:

-gastric emptying latencies
-body weight
-genetic responses to medicines
-erratic blood plasma levels
-how drugs alter our brain structure and other neurotransmitters, hormones,etc.

The blood plasma levels are the key player in on/off. If you find that you need to take more meds than your peers, it could simply be your metabolism to the drug. Still, doctors and other PWP will act as if you are at death's door. I still have the same clinical benefit from levodopa that I did four years ago despite taking on another symptom. I choose to overlap my doses to stay "on" as much as I can.

Some key findings. Note they are all European. Wonder why that is? Wonder where the studies are for the claims it is all due to disease progression?



“On-Off” Phenomena Related to High Plasma Levodopa.

Blind evaluations of transient attacks of dysphonia revealed an association between episodes of neurological deterioration and exceptionally high plasma concentrations of levodopa shortly after ingestion. These results indicate that “on-off” phenomena can be toxic reactions to levodopa rather than deteriorations due to inadequate intake or absorption of the drug.

Levodopa peripheral pharmacokinetics and duration of motor response in Parkinson's disease.


Wearing off occurred when the plasma levodopa level had fallen to approximately 50% of peak concentration, irrespective of the duration of the motor response. Whilst the amplitude of motor response to levodopa is likely to be modified by alternations in dopamine receptor stimulation and sensitivity as the disease progresses, it is proposed that the duration of response is primarily determined by levodopa peripheral pharmacokinetics rather than by central pharmacodynamic factors associated with dopamine storage capacity.


Clinical and pharmacokinetic comparison of oral and duodenal delivery of levodopa/carbidopa in patients with Parkinson's disease with a fluctuating response to levodopa.[/B]

There was a threshold plasma concentration of levodopa associated with the "switch on or off" effect. In addition, rapid attainment of this critical plasma concentration was associated with a quicker onset of action and a more prolonged clinical response.

Just food for thought.

Laura