Drs William G. Ondo and Rajesh Pahwa analyze the pharmacokinetics of different formulations of amantadine for treatment of dyskinesia in Parkinson disease.
Daniel E. Kremens, MD, JD: We’ve mentioned that there are a couple of different formulations of amantadine. There’s amantadine-IR [immediate release], amantadine-IR/ER [extended release], and amantadine-DR [delayed release]/ER. I think we have the most robust data for amantadine-DR/ER. Bill, would you like to say a little about how we think amantadine-DR/ER works?
William G. Ondo, MD: Amantadine-DR/ER is formulated to have an extended duration or longer area under the curve for amantadine. It’s dosed at night and will have its effect throughout the next day. So, it’s already in your system when you wake up in the morning and take the first dose of levodopa. It is presumably the longest-acting version of amantadine, and as was mentioned, has by far the most data. The regular amantadine-IR/ER was FDA approved simply as an extended-release pill and didn’t have independent studies with Parkinson disease. Then traditional amantadine-IR, which has been around for decades since I guess the late 1960s, early 1970s, also has very minimal data and hasn’t had multicenter trials as are done in the modern era. The biggest difference is the formulation, the release, and the fact that by far we have the most data for Parkinson disease, both for dyskinesia and for OFF time, with the DR/ER preparation.
Rajesh Pahwa, MD: I think we also need to keep in mind that even though we have the most robust data, the challenge with the data out there is that amantadine-IR, yes, it has shown to reduce dyskinesia, but it has not had data showing reduction in OFF. Similarly, amantadine-IR/ER shows that it reduces dyskinesia but not OFF, even though they did a well-designed, well-controlled study. It comes down to amantadine-DR/ER is the only preparation that has shown to reduce both OFF time and dyskinesia. Now why is that, because chemically they are all amantadine? We do not know. Is it because amantadine-IR and amantadine-IR/ER, they’re similar drugs except one is a once a day and the other is 2 or 3 times a day? Or is it also the shape of the curve, that when you give amantadine-DR/ER, you give it at night, and like Bill said, when they wake up in the morning, their levels are pretty high and they are starting to have antidyskinetic benefits as soon as they wake up? But there are also data showing that they may be having different benefits, especially as far as OFF time is concerned.
Transcript Edited for Clarity