A riddle, wrapped in a mystery, inside an enigma!

I currently take 4 doses of c/l IR + c/l CR + entacapone on 3 hour intervals...

Recently I skipped dose 4, and I found that dose 3 does not wear off for 6.5 hours!

I have 2 theories at this time:

1. the effectivness of the entacapone increases with each successive dose

2. one of the other drugs I am taking (i.e., sertraline, doxazosin, finasteride) is somehow increasing the availability of levodopa

Has anyone who is taking entacapone noticed that levodopa availability increases with each successsive entacapone dose?

Has anyone noticed a change in levodopa availabilty when taking sertraline, doxazosin, finasteride?

[Gioc]

I don't know if it's relevant to your question, but it sounds interesting.

academic.oup.com/brain/arti...

[Hidden in reply to Gioc]

It looks interesting, thanks!

[Zella23]

I was interested to read your above post as I think some of the additional meds my husband takes prevents the breakdown of C/L making it last longer.

He takes 3 x C/L iR a day and a half dose in the evening, and once a day, Rasigiline and terrazozin (for enlarged prostate).

Rasigiline made a huge difference to the length of time the C/L lasted and enabled him to reduce from 4 C/L to 3. Maybe the terrazozin as well but as he started them both at the same time it’s difficult to tell.

He doesn’t have a particular defined on and off time and frequently takes his C/L later than planned.

Takes Amantadine as the above can cause dyskinesia.

I think it might be the other meds you take making your C/L more efficient.

[johntPM]

In my opinion, there's probably a number of things going on, these include:

Pharmacokinetics (what the body does to the drug): a dose interval of 3 hours with L/C/E gives you higher peaks with each successive dose during the day. This means that the last dose has more to burn off before going below the "on"/"off" threshold. Which, given a half-life of about 90 minutes, translates into more "on" time.

You can see what is going on by using my graph app:

parkinsonsmeasurement.org/t...

You enter the time of each dose and its size, and the app graphs estimates of levodopa plasma levels over time. (N.B. for L/C/E use Stalevo).

Also food eaten could delay and/or slow gastric emptying and the absorption of the levodopa.

[Hidden in reply to johntPM]

Thanks johnPM... Your tool has helped me quite a bit (and I am very thankful for it!), but I don't think it will validate a 2x increase in on-time between successive doses.

Which raises a new theory, the 3 hour on-time dose before the 6.5 hour on-time dose, is potentially greater than 3 hours... I think today, I may let that dose ride, until it is clearly off, and see how long it lasts...

[GymBag]

There are many, many factors that come in to play and it is often difficult to maintain long term consistency. How much stress, level of exercise, foods eaten, bowls regularity , sleep achieved etc at any given time. I found that when I changed any thing it snowballed . If you can get consistent results then you have achieved a great deal.

[Kia17 in reply to GymBag]

Well saeid GymBag.

[Hikoi]

Levod,

If I read correctly you take carb/lev immediate release and controlled release together 3 hourly. Surely you take both drugs for a reason? The controlled release has an average time of action of 6 hours. Add entacopone and time increases plus some of the other factors mentioned here.

Wouldnt taking a long acting and short acting drug together have something to do with it?

[Hidden in reply to Hikoi]

Hi Hikoi:

>Surely you take both drugs for a reason?

Indeed, IR to get quicker response (most important on the first dose of the day!), and CR to get a longer response.

>The controlled release has an average time of action of 6 hours.

I am not sure what you mean by this. My view is that the "time of action" is not fixed. It depends on the CR dosage amount and the patient's therapeutic threshold. Btw, this can be easily seen with johntPM's tool (see his post above)...

>Wouldn't taking a long acting and short acting drug together have something to do with it?

Well the amount of IR and CR certainly have something to do with it, but I have been taking combinations of IR and CR for years, and my inter-dose times have slowly decreased (now 3 hours), and I have never been able to stay on for 6.5 hours with a single dose. And I suspect there are not a lot of PWP 5 years after diagnosis who get 6.5 hours of on-time with a single dose.

[Gioc in reply to Hidden]

Levod, this same drug combination of levodopa was recommended to me by dr C but with the Madopar. Unfortunately, the Madopar version of the CR is quite unpredictable in terms of action times and bio availability because a lot of it is dispersed without being assimilated. It would appear that the C / L CR is similar to the Madopar CR in response, from what I have read and not always linear.

[Hidden in reply to Gioc]

Hi GioCas, I would guess they are very similar... Anyway, I have always seen the CR versions as a kind of "whipping boy" for dietary protein (which I guess is the main contributor to variations in c/l effectiveness)... i.e., I find the closer I watch my diet (as far as protein is concerned) the better CR looks/works! I agree, this is not very scientific, and certainly it's not hard to imagine other potential and real significant causes of variations in CR effectiveness...

Btw, I currently split my CR tablets in half before I take them, thinking this will improve their performance (yes, I realize by doing this it make the CR a little more IR)... And note well, I have never heard this recommended by any doctor or research scientist (in fact I think the drug instructions may say to not do this), it is just my crazy idea...

[Hikoi in reply to Hidden]

Thanks for your reply Levod, interesting. I have taken a combination of CR and IR for a long time. Worked well for a while but then i got dreadful on/off phases. Just stopped the CR this week so early days but feel much improved.