What is the initial starting dose of carbidopa/levodopa, and what is the range of CD/LD formulations currently available for PD? Why does the eventual onset of motor fluctuations and “wearing off” observed over time present opportunities for consideration of scored, fractionated dose formulations of CD/LD?
for initial therapy in Parkinson's disease, it depends on the patient very much what you start. Some patients require levodopa when they walk in the door because they're down the road and have significant symptoms of slowness and tremor resting tremor and rigidity And Levodopa has been the gold standard of therapy for Parkinson's disease for 40, 50 years now. And um The problem with Levodopa is that it has a very short half life. It's about 90 minutes or so in the body and developing therapies that are more continuous has been a goal over many years to try to treat patients with Parkinson's, there's been, excuse me, there's been periods of treatment of Parkinson's disease where levodopa fell out of favor as initial therapy and doping agonists were used for a long time, but I think the pendulum has swung back towards levodopa as initial therapy for most patients. Um the carbon levodopa um that we have today is the same formulation that's been around since the 1970s, early 1970s, but we've improved it in in some forms with fractionated levodopa. Uh And we have also a delayed release or extended release levodopa preparation as well, which is in capsule formulation. So an early Parkinson's patient will come in and start typically on carbon levodopa 25 100 T. I. D. Classically for treating their pockets and symptoms, their motor symptoms and initially they have what's called a honeymoon phase, The honeymoon phase is where you experience nice response and smooth benefits throughout the entire day. Despite taking it just three times per day, usually before breakfast lunch and dinner patients with Parkinson's tended to live in the honeymoon phase for months to a couple of years or three years, uh depending on the patient and then they began to have wearing off classically, is the first symptom of motor fluctuation. That's where their medicine doesn't last quite as long between doses uh and they wear off with tremor, slowness and rigidity returning before their next dose is due. Wearing off can happen relatively quick quickly in less than a year and a study that was done and published in the journal Medicine. Um Uh there was folks who actually had 16% chance of wearing off by less than a year and by five years half of patients have wearing off. By 10 years, 90% of patients have wearing off with their immediate release Levodopa. So that's a problem that we're trying to address and get better at delivering, leave it open a more smooth fashion, uh extended release carbon levodopa has been helpful in that realm. It's in capsule formulation and it gradually release is different concentrations of levodopa over time, where the peak dose lasts out to four or five hours and is smoother for patients. So, so that's been very good
