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Ernie and others: Question from Ernie: ... I was on 1 tablet CR (50/200) twice daily, ... my neurologist thought I was under medicated so suggested I add an extra half tablet at lunchtime. I was only filling in the gap not INCREASING the dose. Have I put this clear enough? I don’t think there is a Sinemet CR 25/100 in the UK. Comment: I do not know what is available in the UK. In the US there is 50/200 and 25/100 in the CR formula. It sometimes gets confusing talking about 25/100 as it is available in both regular and sustained release. There is also the 10/100 and 25/250 regular Sinemet. Every patient should have some 10/100 Sinemet tablets available. I will not go into the reason in this message. You are correct about the release of medication in the CR formulation. The release is a function of the surface area. For this reason a CR (50/200) broken in two increases the surface area and actually erodes quicker. In studies this shortens the time to peak plasma level and actually increases the peak plasma level. The duration of benefit is slightly shorter. Newly diagnosed I want to make a comment on the newly diagnosed use of Sinemet CR which is Ernie’s case. One of the emerging strategies is to start a recently diagnosed patient with one or two CR daily. It is not important that a gap may result between doses. Recently diagnosed patients have the ability to store and regulate release of excess levodopa. This function slowly decreases as the disease progresses (or so it is assumed). The regulation of release smoothes the delivery and the smoother delivery rate of CR to the blood seems to be the best of both worlds. It is hoped this will delay the time when the progression of the disease reduces this storage and regulation. One way of experiencing the storage is to evaluate one's status first thing in the morning. During the night, a reduced level of levodopa seems to be needed. As such, it is assumed that excess production is thus stored for the waking hours. Often patients say they are awaking feeling better and "not needing medication" for a few hours. This does not mean you should not take the morning CR. It is important to always take medication consistently and on time. Your strategy of two CR daily with a half CR boaster around noon is perfectly justifiable approach. This follows the circadian rhythm which has a second low point in the 1 -3 PM time frame. This valley has nothing to do with what you've eaten for lunch. It is a natural low that is 12 hours after the night time low. Believe it or not, the hours from 3 PM - 8 PM are expected to be the best hours for us. (They are not my best hours. I might add my previous post was written from midnight to about 2 AM which is the low-low point in the circadian graph.) My own experience of taking Sinemet for 12 years might shed some light on what I am trying to say. When first diagnosed in 1984, I was told to take Sinemet 25/250 tablets, 3 to 5 or 6 a day and I would feel better. I did and I did. As I look back these tablets were providing high peaks, a real BANG - BANG to the brain. In December of 1985 I returned from Thanksgiving Holiday only to be told the whole division was being axed. My job was terminated as of Dec 31, 1985. By acting quickly I networked employment with a startup company. I was expected to fly to the home office in Dallas and do 7 one-hour interviews with the vice presidents and president of the company. I flew into Dallas the night before but got little sleep. There was a two hour time difference from the West Coast. This meant I started my interviews around 6:00 AM my time. I was nervous, the medications were not working properly. I started with a 25/250 about 7:00 AM Dallas time. I had a short break in the first interview so took another 25/250 about 8:30 AM. Still nothing. I took a third 25/250 at 9:00 AM. Still nothing during this hour interview. I began to lose my faith in medicine so I took a fourth 25/250 at 10:00 AM. It was around 10:15 that all four of the tablets must have decided to work. I had to keep my left arm in a pocket or it was waving down people I didn’t know. I actually sat on my left leg or it would have done a walking tour of Dallas. Through all this I was expected to ask intelligent questions and impress the management that I was the right person for the job. The only question I wanted to ask was, “Can I go now?” I made it through the day and got the job. I will never forget that experience. I could have damaged the brain due to the overload. I started to have regulation problems in 1987 only three years after diagnosis. At that time, the sustained formulation was not available. In May of 1991 I participated in a research study where liquid Sinemet was pumped directly into my small intestine. The pump would deliver LS every 30 seconds. This was a very controlled release method of medication. I was not dependent on erosion of a tablet. The study concluded that (1) if blood plasma levels of levodopa varied, patient response could be unpredictable and (2) if blood plasma levels of levodopa were constant, patient response would also be constant and predictable. These results and earlier results showing similar findings were the target of the marketing of Sinemet CR. A tablet that depends on erosion factors of the gut will never be as good as the infusion system. My system is mechanical and these things do not last forever. I have dropped the pump in the toilet and dried it with a hairdryer. I use a single IV bag for about 6 months. The hospital uses them once. It has been 5 years since I started infusion. One finding that is very important, is that after five years, those still using infusion have not varied their medication level by more than 5 - 10%. The disease has progressed in the five years, but the medication levels still stayed the same. This goes to show that a smooth delivery is beneficial in long term levodopa therapy. I am not convinced the CR formulation meets this requirement. I will not go into the use of agonists, but this is where this drug class can be beneficial. I hope this gives a better picture of benefits and pitfalls of levodopa therapy. Regards, Alan Bonander