Hammilton, quite rightly asks what frequent dosing has "to offer over an extended release formulation?"

Controlled release drugs have a role to play: they can get you near the right level of drug concentration and hold it there for several hours.

For patients with functioning dopaminergic neurons excess levodopa can be stored, converted into dopamine and released as required later. In this way the peaks and troughs can be levelled off to a large extent.

As the disease progresses dopaminergic neurons die off or cease to function correctly. The storage capacity is, therefore, lost. This leaves you following plasma levels of levodopa: too little and you are "off", too much and dyskinesia can occur.

At this stage, the longevity of the controlled release drug counts against it; it's been taken and will continue to deliver levodopa regardless of the present requirements.

Another problem is that most drugs come in a limited number of strengths. It will be rare for a person's requirements, based on body weight, diet, exercise etc., to be optimally met by one of the strengths available.

Let's make a rough estimate of the size of the discrete strength error. For instance, Stalevo comes in six strengths: 50, 75, 100, 125, 150, 200 mg levodopa. Suppose you relied only on one 100 mg pill taken four times per day, making no adjustments. And assume this really was the best strength for you to take. Roughly speaking this means that your real need lies between 87.5mg (half way between the strength you take and the strength below) and 112.5mg. So, the error goes from 0 to 12.5mg, giving an average error of approximately 6%.

High frequency dosing allows adjustments to be made to fit patients' requirements.

John