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Bob Howard: Based on your definition of pill requirements for your wife, I would guess she is taking 10 - 15 of the Sinemet 25/100 rgular. If so, she may be expeeriencing carbidopa tocity. When carbidopa exceeds 200 mg daily for some reason levodopa seems to lose much of its value. If you throw in all the other possible factors that can effect pill procesing, anything may happeen. I would suggest she start the day using 25/100 pills, but limit it to two pills. The rest of the day use Sinemet 10/100 regular. I think she will find the medicine much more effective and her needs for sinemet reduced.. The objdective is to keep carbidopa between 75 mg and at most 200 mg daily. The best target is around 100 - 125 mg. If this does not work (try it for about two weeks) she may need to go to liquid sinemet. One other possibility is that she has some depression. This can limit the effectiveness of all drugs. Regards, Alan Bonander ([log in to unmask]) San Ramon, CA (near San Francisco)