Levodopa absorption

[gesundheight]

What makes absorption of the last (evening) Levodopa dose very poor regardless of the last meal taken before, or even on empty stomach?

[camper1]

I wish i had the answer but if I eat anything my medication doesn’t work for hours after.

[koshca in reply to camper1]

The same

[Gcf51]

As I understand, one of the reasons to take levodopa on an empty stomach is you may have bacteria in your gut that will feed on levodopa and therefore have less levodopa available to be absorbed.

[Trig27]

this is a complicated subject, levodopa is transported from gut to portal vein using similar mechanisms as other amino acids, so protein in the gut can effect levodopa absorption.

see: ncbi.nlm.nih.gov/pmc/articl...

also, some levodopa is converted to dopamine in your gut which slows gut motility, so if the patient has consumed both lots of protein and levodopa throughout the day then it would seem plausible that there could still be a high quantity of protein in the bowel interfering with levodopa transport.

also, there is the effect of the microbiome but I have not read of a circadian pattern with respect to how the microbiome effects levodopa.

for a list of papers that discuss levodopa absorption and how it changes over time due to changes in the gut see the papers linked here:

healthunlocked.com/cure-par...

"How do you know the absorption of the last dose is being absorbed poorly?" Is an important question to answer. Some patients get "sundown" but I am not sure that is due to reduced oral levodopa absorption but some other circadian process. Humans have very strong circadian patterns, I would investigate those too.

The circadian pattern of dopamine is very interesting. In normal human serum dopamine actually peaks at midnight and troughs at midday. Opposite of PD patient on oral levodopa.

Subcutaneous pump should alleviate some of the drawbacks of oral C/L administration. Good luck.

[gesundheight in reply to Trig27]

Thanks! Very interesting info. I will have to study this closely. Is the Subcutaneous pump FDA approved?

[Trig27 in reply to gesundheight]

the pump is not approved in USA at this time, Europe & Japan only at present. But keep your eyes open, two companies seeking approval in USA.

[rebtar in reply to Trig27]

I definitely feel that cycle of afternoon slump.

I find that if I take enough meds to keep me going in the afternoon, early evening, my bedtime gets pushed back and I get very little sleep. I keep cycling through increasing meds a tad, and then backing off when I can't sleep, which means being verygroggy and sluggish in the afternoon (like now), and very uncomfortable between last dose around 6, and bedtime.

When I increase dose, I get very impulsive and compulsive, not good.

Going to talk soon with neurologist (MDS), definitely need help to figure this out, I'm not doing a good job.

But to be fair (to me), we're in the middle of moving. Rough.

Rebecca

[Trig27 in reply to rebtar]

yes, it's a tough cycle. oral C/L is a miracle drug, but not without drawbacks

[park_bear]

If you take a supplement containing vitamin B6 around that time that would do it.

[gesundheight in reply to park_bear]

No supplements around that time and last meal is usually four hours before (with. or without protein does not matter)!

[eschneid in reply to park_bear]

PB,.......What is a safe range of B6 to take? For some reason I've never been sure.

[park_bear in reply to eschneid]

Good question. People have reported B6 toxicity when taking little or no B6 supplementation, presumably because of B2 deficiency. See here for detail: healthunlocked.com/cure-par....

As long as someone has abundant B2 and is using P5P there ought to be no limit, but this is not proven. Personally I took 70 mg of P5P daily for 5 years without any adverse effects. I recently dropped down to 20 mg because it's one less pill and I do not take very much levodopa medication - 2 & 1/2 doses of 25 / 100 C/L.

[Boscoejean]

this is not an answer so much as a question- I am wondering if slower digestion in Parkinson's might have something to do with this and if there was still any food in the stomach would it make the absorption less effective even if it is not something high in protein

[johntPM]

You get an indication of whether Stalevo (levodopa, carbidopa, entacapone) has been absorbed by the colour of your urine. Assuming that you've got no other processes going on, the urine is yellow if absorption has taken place and clear if not. You can turn this into a real metric by measuring the colour of the sample using a web cam.

[johntPM]

IJAM, 2021

"Dopamine: a modulator of circadian rhythms/biological clock"

Trig27 (above) writes about the role of circadian rhythms in PD. In this world, one has to add together the dopamine generated endogenously by the body naturally to the levodopa (converted into dopamine) generated exogenously by the medication.

This is important. It may go to explain why, for instance, some patients have dyskinesia at times other than the classic peak dose LID; and why medications sometimes last a shorter time than expected. Drug regimen need to take this into account.

John

Dopamine circadian rhythm.