Dx 6 years ago DBS 3 years ago .
lately take extra dose for some occasions, my body becomes more tense, stiffer and slower no dskynesia though then I take another dose to address it ,sometimes work sometimes don’t, it confuses me,
Does anyone have experience to share?
Yup. Almost certainly. I'm not sure if I read PBs original post on the subject, but if I had I had forgotten about it.In my case complicated by the dystonia attributable to the PD creeping up over time, around the time I was experimenting with the vCR gloves.
And then apparently arriving with a collosal bang when I stopped using the gloves only to ease substantially when I resumed using them
Subsequently I have fiddled with my C/L dose, and with glove use times and thought I detected a distinct window between too much and too little medication. At times quite a small window.
Even so, even though it was obvious and a perfect fit with my experience I thought I was bonkers until I read PBs post. (n=1, no control group... Etc)
healthunlocked.com/cure-par...
And I've just realised there is an added complication, in addition to the "latency" of the levadopa response. This is the unavailability of 25/100 C/L immediate release in France. So, in addition to pramipexole LP once a day, my prescription was 2x10/100 4 times a day. That's 80mg carbidopa a day (and a lot of levadopa). But 80mg is above the threshold usually suggested to be effective. "Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg a day"
I have cut the sinemet as low as 3 times a day 1x10/100. That just gives 30mg carbidopa a day compared with 75mg if I had the same levadopa as 25/100. But even trimming it by just half a tablet for each dose drops me below 75mg.
“If SINEMET 10-100 is used, dosage may be initiated with one tablet three or four times a day. However, this will not provide an adequate amount of carbidopa for many patients” Drugs.com states that at least 70 mg carbidopa is desirable for optimal effect, however I have not come across the study in question. It almost seems like a license letter for neurologists to start with too high a dose of Sinemet. My medication works better than ever after 2.5 years with 4 x a half 10-100, so only 20 mg of carbidopa per day...
My dad worked for MSD and was part of the launch of sinemet. 25/100 was the regular medication. 10 /100 was a fine tuning top-up. Dr Google may no longer have the studies to hand, but at launch the prescribing advice was for daily carbidopa levels to be in the range 75-200. It was (is) recommended that daily carbidopa does not exceed 200mg a day. Which was why 10/100 was manufactured. Recommended starting dose was 25/100 tds. Once the dose reached 2x25/100 qds then if you want to increase the levadopa but stay in the 75-100 range for carbidopa switch to 10/100
It just means that if I increase from say 600mg ldopa to 800 mg ldopa there is an extra "kick" from having enough carbidopa to "fully" prevent it being decarboxylated in the peripheral blood stream. Which means it's not as simple as just adjusting levadopa dosage
Thanks for the history of Sinemet 10/100, It seems that the reach of 70-100 mg carbidopa was more necessary as a safety margin. It is a pity that this research information about such an essential part of PD medication is not available.
That's a very interesting discussion. So am I understanding correctly that there is a sweetspot of daily carbidopa dose of 75-200, below which too much levodopa is converted to dopamine and lost in the periphery, and above which carbidopa is saturated so that further increases of levodopa again only result in an under-proportial increase of levodopa (and hence dopamine) in the brain? Naturally, that's crucial information for proper dosing of the right combination of C-L.
Now the question is whether you need 75 mg carbidopa per se even at low doses of levodopa. I would like to have an explanation for that. My personal experience is that if your levodopa dosage drops that can be proportional to the carbidopa.
Well, personally I seem to require 2x 25/100 C/L three times daily to keep my dystonia under control at the the moment, so I am more concerned with the upper than the lower limit of carbidopa...
Maybe this dosing issue is also related to the FDA concerns re IPX203, which interestingly did not concern the levedopa but rather the carbidopa component: neurologylive.com/view/fda-... ? -- Cannot find quickly though how much carbidopa actually is in IPX203.
It's to do with Carbidopa efficacy and toxicity. At 75mg-100mg daily then it should be sufficient to prevent any levadopa in the peripheral circulation being decarboxylated into dopamine. It's not that it is 100% effective, but adding more carbidopa doesn't achieve anything. 200mg a day was the maximum level authorised. So the goal is to get 75mg, and the standard recommended starting dose of 25./100 tds achieves that. By the same token, the normal "maximum dose" of 2x25/100 qds is 800 mg levadopa and 200mg carbidopa. It's not recommended to take more carbidopa than 200 mg. This is often misinterpreted as a levadopa limit of 800mg. Whereas in fact you can use 10/100 to keep carbidopa below 200mg but ldopa above 800 mg
Eg 4x25/100 + 8x10/100 gives 180mg carbidopa and 1200mg ldopa
Below 75mg daily you ideally want a 1/4 mix, which 10/100 doesn’t give me. So if 1 go from 4x2x10/100 {80mg carbidopa} to 3x10/100x1.5mg the carbidopa is only 45mg, and at 1/10 strength, so some of the ldopa is being wastefully converted into dopamine outside the brain.
Which complicates things...
... whereas in Germany, the standard Madopar is 25/100 C/L, so if you need more than 3 Madopar/day for the levidopa, you go beyond the 75mg carbidopa, which in the long run might also complicate things.
Maybe we can trade. In France only 10/100 C/L IR. I now halve 25/100 C/L ER and that's fine too.
You should be OK up to 8 tablets a day. Indeed I think there have been recent studies showing twice that amount of carbidopa is ok
seems every one having mild symptoms taking so little C/L? I was taking 50/200 mg X 5 daily...
A year ago I took still 20/200 x 5 and the neurologist's advice was a further increase...
got further discussion, my dystonia happen wearing off it confuse me whether is normal wear off or too much C/L
C/L induced Dsytonia - extreme pain. 
Should he increase C/L dosage?
What steps to titrate down c/l safely?
