In France the 1:10 ratio for carbidopa - levodopa is often used. My neurologist idem with Sinemet 10/100 IR. Sinemet 25/100 CR is prescribed only for the night. My daily carbidopa intake due to dose reduction is currently total only about 45 to 55 mg. Now I read in the patient information that “At least 70 mg to 100 mg of carbidopa per day should be provided”.
"As the ratio of carbidopa to levodopa increased, there was a significant increase in apparent t1/2 and AUC values of levodopa....There were less subjective side-effects in the 1:4 groups than in the 1:10 groups. It is concluded that increasing the amount of carbidopa in relation to levodopa may be beneficial ..."
Increase t1/2 (half life) makes the effect of a pill last longer; increase AUC (area under curve) gives you more total effect. A major advantage of carbidopa is that it reduces nausea, by reducing the metabolism of levodopa outside of the brain. It could be that the 70 mg figure comes from that.
No. But I've asked the question twice, and I have an appointment with Christine Brefel on 22 March, and I'm going to dig in, sit on the naughty stool if I have to, and get an answer. I don't think there is a good one. MSD switched the branded product across to slow release, because it had more patent legs than the flagging widely generic immediate release, although its almost universally agreed to be of limited benefit (code for completely hopeless)
At launch, there was tons of stuff about 4:1 being the ideal ratio. At 4:1 the recommendation for switching from levadopa to sinemet was that 100mg sinemet is equivalent to 500mg levadopa. The 10:1 product was introduced as a "fine tuning" "top up" tablet , where you wanted to add 100mg and 500mg would have been too much
The answer I intend to pursue, identified from a comment in Eric Ahlskogs book, which I intend to brandish at my meeting with the feisty Dr Brefel, is Madopar -often called Modopar over here vidal.fr/medicaments/gammes...
It uses Bensesaride instead of Carbidopa as it's DDCI but, broadly they are equivalent. I'll report back. Meantime, if you hear anything please let us know.
I think the 70 mg relates to the fact that at that level, in most people, most of the peripheral metabolism's decarboxylation is inhibited. But it's a fairly imprecise science with a lot of variation between individuals
I mostly split my 100/25 liberation prolongee tablets; the split tablets act pretty quickly for me so I don't need to use IR. I get dyskinesia so choose to spread out a smaller dose. I take a whole tablet at night only. I am assuming the ingredients are more or less equally spread! Good luck with your neuro.
It seems that combining 10/100 IR and 25/100 LP will give an ideal combination. Handi that graph tool from John Turner! However, the problem is that with the current low dosing demand, I have to halve the Sinemet pills and thus the action of the LP will probably change to an IR as you can see from Kevin51's response. Then in Europe, switching to Madopar would indeed be an alternative. They have LP in the low dosage 12.5/50 and IR 50/100. The only difference is the excipient which changes from carbidopa to benserazide. Although "broadly" the same I am reluctant to change especially with reasonably well working medication. Can you convince me or shall we wait for Dr Brefel’s response?
Unfortunately, what I proposed here is probably wrong. In any case, in France there does not appear to be an LP version 12,5/50 from Modopar or from another supplier. I'm afraid that's the case elsewhere too.
Have you had your appointment with Christine Brefel and have you perhaps thought about the question about the recommended minimum carbidopa intake per day? (“At least 70 mg to 100 mg of carbidopa per day should be provided”).
No. Like a complete moron I missed it. Thought it was on a Thursday and it was on the Wednesday. By the time my phone reminded me it was too late - it's a 2 hour drive. The hospital are due to be rescheduling (I'm going to be on the naughty stool again). In the meantime I have an appointment booked for June with another neurologist in Carcassonne. Fortunately I am doing really well at the moment, so not as disappointed as I might have been
I am from Canada and the first offer of Rx is usually the 100/25 IR Sinemet. I had done some research and I concluded that taking Carbidopa might be linked to an increased risk of cardio-vascular diseases, so I opted for the 100/10 IR. I take a total of 6 of these a day.
Could you share that research regarding cardiovascular risk and Carbidopa please. It is contrary to everything I have ever known about those drugs. In the first place, Carbidopa is never used alone, only ever in combination with levadopa. It's sole purpose is to prevent levadopa being metabolised where it shouldn't be. Levadopa , or rather the dopamine it is converted to, in the peripheral metabolism is well known to have Cardiovascular risk. Combining levadopa with Carbidopa gets less levadopa converted to dopamine outside the brain, and more of it converted in the brain, and if anything should reduce cardiovascular risk
There is just no data for carbidopa alone. All the research is for it in combination with levadopa - it's sole function. It's levadopa that causes cardiovascular risk, and that risk is not from levadopa per se, but the toxic dopamine it is converted into in the wrong place. That was the whole point about the Sinemet patent.10/100 instead of 25/100 reduces the benefit for PD and increases the cardiovascular risk
You are right, the information against Carbidopa comes from the Dr. Hinz protocol amino acid treatment of PD, I was following this protocol with Mucuna for 2 years and it was no better than conventional medicine, it was worse because I was nauseous after every dose of Mucuna. I left the program 5 yrs ago and strangely enough I don't find those references to the malicious Carbidopa. Here is one reference 'retracted' : dovepress.com/the-parkinson...
Here is another reference to carbidopa that was made and has been retracted : While carbidopa/L-dopa combinations are the current
standard in medicine, 5-HTP, as documented in Table 1, was
administered in place of carbidopa based on the following
considerations. Carbidopa has no efficacy in the treatment
of Parkinson’s disease symptoms. Its only indication is
management of the L-dopa-induced side effect nausea.11
It is documented that carbidopa irreversibly binds to and
permanently deactivates the active form of vitamin B6
Who does your blood work? Does your neurologist work with you on food and supplements? I'm working with a neurologist and a movement specialist neither one of them ever mentioned anything about b12 or B6.What kind of doctor should I look for that makes the connection about the vitamins and supplements and Parkinson medication? I live in Pittsburgh Pennsylvania I'm having trouble finding a functional medicine doctor who's familiar with Parkinson's and osteoporosis and consider the importance of vitamins minerals and herbs. Any suggestions will be appreciated
Unfortunately, there are almost no neurologists to be found with a holistic approach to each individual patient. Incomprehensible that, with all the knowledge there is today for optimising health, there is not yet integration with traditional and orthomolecular medicine that advises you on a healthy lifestyle with the aim of preventing disease and healthy ageing in combination with scientifically based treatments. I am still looking for a neurologist who is at least open to this, but a consultation with a separate orthomolecular doctor/natural dietician with knowledge of PD and PN seems almost inevitable. From experience, don't wait too long with this. Every day without a consistent treatment plan can cause irreparable damage. For example, a neuropathy can still recover if more than 50% active nerves are still present. Do not accept the familiar final phrase "I will see you again in 6 months" if the cause of any symptoms have not been found and further investigation is still possible. The necessary blood tests are ordered by my GP or neurologist (at my insistence). The vitamin tests are at my own expense, which shows how little value is placed on this....
Or does it actually appear to be a maximum if I also read “Peripheral dopa-decarboxylase may be saturated by carbidopa in other carbidopa/levodopa products at 70—100 mg/day, which produces equivalent exposure to 140—200 mg of carbidopa in the extended-release capsules.”Who can explain the meaning of this? For me this is topical again because this month my C/L medication has been reduced to 20/200 IR per day. That works fine, but what would possibly be the benefit of taking half pills ER which actually gives you 50/200 IR per day?
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