Brian Collins wrote: > On Sun 25 Jul, M Potter wrote: snip > > This may seem like a silly question but I'm trying to learn all I can. > > So, who better to ask than you, the experts! My mother just recently > > began taking Sinemet, I wrote to you asking about the nausea problem > > before. She is taking the 50/200 dosage, she asked her doctor about > > cutting the pill in half and he said "no" that it isn't the dosage of > > the med making her sick but just the "nature" of the medicine. The silly > > part of the question is can a controlled release pill be cut in half > > (someone told her that you shouldn't) and if you do cut it in half does > > it become the 25/100 dosage? > > > > What she would like to do is start out gradually with this medication. snip > The important parameter when dealing with Sinemet is the rate of flow of > the levodopa (that is the active ingredient) into the brain. For most > people, a tablet of Sinemet 25/100 (100 mg of levodopa) lasts about 2 > hours; a nominal rate of flow of 50 mg per hour. > > In the CR version of the Sinemet, the body of the tablet is designed to > disolve at a slower rate. Typically a CR tablet will disolve in 4 hours, > giving a nominal flow rate of - 50 mg/hour, just like the other tablet! > However, it lasts twice as long, which is more convenient. > > Now consider what happens if you break the tablet along that tempting > weak spot across the centre of the tablet: You open up two more surfaces > of (at a guess) an extra 20% of surface area. giving a faster rate of > erosion of the tablet. The net result is that although you set out to > produce two CR tablets each giving 100 mg at a rate of 25 mg/hour, > you end up with two tablets, lasting about 3 hours and 12 minutes, > and giving a higher dosage than you intended, at a rate of 60 mg/hour > which is a more powerful dose for a shorter time. snip I prefer the usual pharmacokinetics calculation of levodopa concentration in the blood plasma rather than Brian's flow rate approach. this is somewhat discussed on my website. i recommend perusal of it, but this requires a current browser, so i am going to include some of the words only here. optimizing medication schedule infusion of levodopa from a pump into the small intestine at a constant rate was touted as the best way to achieve uniform, continuing ON state by Alan Bonander. intravenous pumping would also be a way to get a constant supply of medicine. neither of these is something that many of us wish to put up with, however. taking liquid or tabletted medication is usually less trouble and expense. Dissolving the day's doses in a container and drinking aliquot amounts every two hours or hourly can also approximate constant flow of levodopa into the bloodstream. this too is quite a bit of trouble to prepare and remember to ingest so frequently. Bob Naylor used graphical addition to optimize his wife's medication. I adopted his idea and have had some graphs available on a sub-page. the information that Alan sent me is also available on a 2nd sub-page. Brian Collins continues to innovate his approach which is on a 3rd sub-page. Bernard Joly has introduced his meg07 Excel spreadsheet approach. I have not the software to use it. I spent some hours trying to glean best data for the primary tablets taken by us to alleviate the symptoms. there is not a lot of information available to me. there is wide variation in the measured concentration of levodopa in the bloodstream following ingestion. in spite of the variability, I believe there is value in helping a patient know the basic factors of the pharmacokinetics. this graphic addition using a smoothed curve from Bob Naylor's original for regular Sinemet 25/100 tablets taken at 3 hour intervals shows that 5 micrograms levodopa per deciliter of blood is reached about 15 minutes after taking the first pill. the concentration remains at or above that value until midnight. If the deficiency for this patient is provided by that amount, the patient will be able to function all day. the use of 3 Sinemet 50/200 CR tablets can provide this same level of medication if the best guess mean blood concentration data is valid: the time to reach 5 micrograms per deciliter of blood is reached about 30 minutes after taking the first pill. less efficiency from CR tablets results in the 5 micrograms per deciliter at about 7 PM. This best guess curve is significantly more spiked than Bob Naylor's curve shape for the same CR medication. Either regimen will suffice - except that the evening hours will be sub-par for the latter. The peaks and valleys cannot be avoided entirely unless a metering pump is delivering the medication. If one takes the trouble to prepare a diary of how s/he felt and functioned all day at half-hour intervals - and records the time accurately for each evaluation - and also notes exactly when and how much medicine was taken as well as noting when food and drinks were taken - with some detail of amount of protein especially; then, study of this information can yield improvement often. If the data is enhanced by not following the same schedule for a couple of days is also done with similar note taking, further insight may result. For newly diagnosed patients, the thing to remember is that the half-life of the two types of medication is different. Taking six regular carbidopa/levodopa tablets (or portions thereof) is optimal due to the approximately 3-hour half-life. The slow-dissolving tablets should be taken as quarters or halves or three-quarters, or whole per their approximately 4.5-hour "half-life" schedule also. (the warning to not break them is not valid advice unless one goes beyond quarters.) If you get relief from your symptoms taking one-quarter of a 25/100 tablet 6 times per day, that is the dosage you should take. If you need a half each time, use that. the logic behind minimization of intake is that the eventual dyskinesia is usually blamed on the spikes. those of us who have to take more to provide enough will have to be more schedule-bound or live with wavering functionality. If there is less than 70 mg. of carbidopa in your daily intake, get some of the carbidopa only tablets to increase to that amount each day. blood plasma levodopa concentration data versus time from ingestion is sparse. most of the data comes from the november 1989 NEUROLOGY 39 (suppl 2)article on pages 25 through 38. i have used the best guess label for my baseline which incorporates all the mean and standard deviation informat in that article which is the summary report of the human trials data. unfortunately, there is very large deviation in all the CR data. you may see the graphical depiction of the data in several comparison plots at: http://www.ridgecrest.ca.us/~rfvetter/pages/levoplas.html persons who wish to see specific examples of graphical integration/addition using several medication schedules (which ignore food intake effects) may ask me to send them attachment of some in Adobe Acrobat .pdf file format. please see my PD subpages first even though the depth of the verbiage is technical. this information is not validated by any professional. it is believed by myself to be valid mathematically correct and valid, but is nearly random in variability measured. ... ron -- Ron Vetter 1936, '84 PD dz [log in to unmask] http://www.ridgecrest.ca.us/~rfvetter