"Off time” may vary in severity at different times during the day due to physical activity and other factors, does this support the need to have different dosing options available in the manner provided by a scored, fractionated formulation of CD/LD?
um of all the levodopa preparations are all the ways to address motor fluctuations. One of the more practical option is the fractionated scored levodopa. So we have the levodopa tablets which we're very familiar with its and 100 mg formulations. But the fraction it's called levodopa is scored in three times and therefore it gives the clinician and the patient the ability to deliver 25 mg increments of levodopa. So then you have nearly infinite combinations of levodopa, 25 50 75 101 25 1 51 75 et cetera. And so when a patient is either has non uniform motor fluctuation. So for example, they have more wearing off at certain times of the day and less at certain times of the day, which is fairly common in Parkinson's, that's the time to consider when they have very brittle motor fluctuations is another scenario for what do I mean by that, when you give a little bit more than they need to or they want, then they become very dis kinetic. And if you give a little less than they need, they become very off and have this horrible feeling, whatever that symptom or constellation of symptoms are. So for those brittle um fluctuate ear's, then the fractionated scored levodopa is probably the way to go because you could really customize it to the 25 mg increments. Um I have a patient, for example, one patient gets incredibly dis kinetic with even a half a tablet of regular cinema, which is 50 mg. So what they actually need. What that patient needs is 25 mg, Which is nearly is very difficult to do on the regular levodopa tablets because they'll need a pill cutter to cut the half in half again and it could crumble. It could give inconsistent dozing. And so when that occurs, some of the 25 may be more effective than the other 25 mg. Whereas in a fractionated scored levodopa, You can be assured the patient doesn't need a pill cutter. They just cut it, split it with their hands and they'll get 25 mg every single time. It's not uncommon for my patients to have need Only 25 mg every three hours or every two hours Because 50 will make them this kinetic and zero will not make them move at all. And so they do need 25 every two hours every three hours. And so the fraction of it scored Levodopa would be a savior for this patient. Another scenario, as I mentioned, is a patient who say, requires 125 mg for the first two doses, but requires 75 mg for the third and the fourth dose. And so using regular levodopa may not actually make it quite complicated for this patient, but using a fraction at its core levodopa would make it very convenient for this patient. Now, not all my patients have the ability or the freedom to fraction eight there Levodopa as they please. So this is where the art meets the science and getting to know your patients well. Really come in the picture. So I have longstanding Parkinson patients who know their bodies very well and they're very trustworthy and they know exactly when to take their leave it open and how much those and they're wearing off symptoms are quite distinct. They function almost normally when they're in the on state and they're devastated when they're in their off state. Um Whatever motor or non motor symptoms that can be causing that for those patients, you could give them some freedom some range whether it's you could go from a quarter to three quarters depending on how you feel on this, let me know what it is. So that my my record would be consistent with what you're actually taking. Um Now some patients may not have that degree of discernment of their on and off states and therefore they will lean towards you to you to do the fraction ating of their levodopa and the adjustments. So you will have to ask them what exactly they feel when When they take their first dose at seven a.m. Uh And what you know ah when do these symptoms start getting feeling better? And how long do they last if their next dose is at 11 a.m. How are they at 11 and then it is up to you to kind of infer that that patient is experiencing either delayed on or wearing off on the first dose and then you go now with your 11 so you take your 11 o'clock dose and your next doses not until what 03 p.m. Doctor. Okay so Do the symptoms get better when you take your 11? No not until around 1145. Do they last until three p.m. O. They start falling short around 2 30. So then you have that information and you could then make levodopa adjustments for that. So in some of my patients it is a most of my patients it is a joint decision as to how much to fraction eight for each dose. In some of my patients they actually have the ability to make some adjustments within a range. And in some of my patients I have to do all the adjustments providing after the information that they give me. So again not one size doesn't fit all, not only with regard to their symptoms but also how you treat their symptoms.
