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I appreciate the interest shown in this topic. A special thanks is due Kathrynne Holden for line by line responses to all the items I asked about, as well as to Ron Vetter for the "introduction to pharmacokinetics" and those informative graphical representations. I have begun supplmenting what you kind folks have told me with a few pieces of information I've started reeling in while fishing the Internet. What I'm finding suggests to me that any attempts to fine-tune dosages aren't worth a hoot in a gale of wind without taking into account the gross realities of the digestive system. I'll describe some of what I found in the hope of enticing people better qualified than I to interpret some of this stuff. As it turns out, now I have even more questions than before, especially about what happens to the larger dose of sinemet CR. First, there is a description of the workings of the digestive system in an e-text booklet from Colorado State University: http//arbl.cvmbs.colostate.edu/hbooks/pathphys/digestion/index.html Two states of the system are described that have widely differing influences on oral medication. 1) digestion - the processes that are initiated starting with food intake, and 2) the interdigestive state, during which there occur 2a) periodic series of housekeeping contractions known as the migrating motor complex, which alternates with 2b) quiet times. 1) During and after a meal the stomach grinds the "ingesta" by means of contractions. As these occur there begins a process of gastric emptying into the small intestines through a sphincter called the pylorus. The booklet says solids must be reduced to a diameter of less than 1-2 mm before they pass through the pylorus. This immediately raises a question --what happens to the 50/200 size of sinemet CR in this process? A large CR needs a slit of about 3 mm to get through the flat way. Emptying the stomach is regulated by a feedback mechanism in the instestines. When fats are detected signals are sent back to the stomach to slow down its activity. This in turn slows down gastric emptying. No timings are given. How long can gastric emptying take? What is the effect on drug delivery of various proportions of dietary fat? A large class of water passes into the small intesine quickly, because there are no solids to grind. What happens to pills - do they get swept through the pylorus along with the water? Ingesting only a very small quantity may not stimulate gastric activity. A degree of gastric distension from volume of contents is needed for that. This seems to suggest that taking one's pills with just a swollow of water won't be sufficient to get them to the small intestine where they will be absorbed. 2) Between meals the migrating motor complex recurs every 1 1/2 to 2 hours. It is a set of contractions that start gradually and build in intensity over the course of about 1/2 hour or more. These contractions empty the stomach of remaining solids which hadn't made it to the small intestine, and sweep them along through the intestines. Now some more questions. The usual recommendation I hear for taking PD medications is 30 minutes before meals. Is the idea here to get the pills into the small intestines before beginning the next meal? In light of the above discussion of intradigestive cycles, what happens to pills after taking them at this time? What difference does it make whether or not MMC activity is occurring? What about regular vs CR sinemet? Which gets through better? -- continued on part 2 --