Pharmacology of levodopa/carbidopa

[Spottedtowhee]

I’m hoping someone can explain the pharmacology of l/c which has never been explained satisfactorily to me. I’ve been taking l/c for two and a half years and was diagnosed coming up to eight years ago.

I understand the half life of levodopa is one and a half hours. But there still seems to be some effect for 12 or 13 hours after my last dose. I take 100/25 every 2 to 2 1/2 hours starting at 9 AM with my last dose at 6 PM.

Before I started medication I couldn’t roll over in bed or get out of bed in the middle of the night. But on the medication, even though I haven’t had a dose in several hours, I’m able to roll over and get out of bed with minimal effort so there has to be some residual effect and I would like to understand how.

I would also like to understand why it is that my arm and hand function is much improved on the medication but I am now starting to have trouble walking especially during the 12 hours off medication, but also somewhat during the 12 hours when I’m on medication. Yet my hand and arm function remain quite good.

Thank you for your help.

[johntPM]

A very good question.

You can split the answer into three parts: short duration response pharmacokinetics, short duration response pharmacodynamics; long duration response pharmacodynamics.

Pharmacokinetics means what the body does to the drug. This is where the figure that you give of the 90 minute half-life of levodopa comes from. 12 hours is 8 half-lives so, on this basis, we would expect a response of 1/256 of the original power.

Pharmacodynamics means what the drug does to the body. This better represents your examples, e.g. walk/no walk. I can see a number of reasons why in this case the pharmacodynamic response does not exactly follow the pharmacokinetic response. Your body is still producing dopamine (endogenous), so the levodopa is adding to this with exogenous dopamine. Now, many tasks, varying from person, are almost like switches in that over a short period of time you can go from near normal performance to rubbish . In these cases, the exogenous dopamine caused by the levodopa can have disproportionate effects. Also, you need to take into account the reservoirs of dopamine found in vesicles in surviving dopaminergic neurons.

Regarding, better performance in some motor activities than others: with no evidence, I've always put this down to luck as to which neurons survive and the use that we make of a particular movement.

Some people claim that there is, in addition to what we talk about above, a long duration response to levodopa of a similar size to the short duration response.

You can see your response to levodopa by doing the side-to-side tap test every 10 minutes over a period of about 4 hours. My home page contains a graph showing the effect a dose of levodopa has on me.

parkinsonsmeasurement.org/

A computerized version of the test can be found at:

parkinsonsmeasurement.org/t...

[aspergerian in reply to johntPM]

Excellent delineation! Thank you.

[Spottedtowhee in reply to johntPM]

Thanks for the detailed and clear explanation.

[GymBag in reply to johntPM]

Good question , good explanation. interesting web site. I did similar studies of my response to PD medication over the years, manually with pencil and paper and found that there are too many variables coming into play. Time of day, last food eaten , food eaten yesterday, bowels , how well urinary system is cleaning the blood, how much sleep , how much exercise, mood, . Its a very long list. Watch the color of your urine change as the day goes on.

[Stazina]

In short Levadopa is able to pass through the blood brain barrier (the protective part of the brain) to help you make more Dopamine which controls movement. Carbadopa is added to it to control the Levadopa so you don't get too much at once.

[Spottedtowhee in reply to Stazina]

Thanks, Stazina.