Impact of Levodopa Absorption on OFF Episodes in Parkinson Disease


Drs Laxman Bahroo and Sanjay Iyer assess the potential variability in levodopa absorption in the gut and its impact on OFF episodes for patients with Parkinson disease.

Laxman Bahroo, DO: We know levodopa is the most effective treatment for Parkinson disease, but there are variability issues. One of the biggest things with levodopa is that it needs to be absorbed. I had this conversation with my patient today, and she said, “I take a good amount of dosage of levodopa,” she’s on even an extended-release formulation, and “and I take it on time,” and she has an alarm clock, and even with this, some doses work and others don’t. I said, “Well, then there are 2 factors. If you’re taking your doses consistently and on time, then it comes down to, is your activity different throughout the day?” In other words, is your need for medication different throughout the day? That’s one possibility. The second possibility is your gut doesn’t absorb or doesn’t move as much across the board, or what are you eating in between, not every meal is identical. There’s that variability based on the gut in terms of absorption, the mobility of the gut, the food intake, and even activity. There’s a lot of variability with levodopa that we’ve seen, especially with advancing Parkinson disease. We don’t see this in early Parkinson disease, and I suspect we don’t see it because you need a lower dose to turn ON, you’re in that honeymoon period, and you need it about 3 times a day. But when you’re getting to 4, 5, 6 times a day needing medication, and the gut is getting progressively more impaired, as is the rest of your body, needing more medication, you need more and more frequently, and the gut isn’t working as well as it should, then the reliability of levodopa becomes less. So we have to talk about rapid, reliable treatment options that can bypass the gut, or using on-demand therapy that bypasses the gut, or even adjunctive options.

This is when you enter the discussion and say, “Look, we have you on a cocktail of levodopa plus/minus standing medications. Maybe this is a time when we adjust just those, or talk about on-demand therapies.” I would call it a pivot moment in Parkinson disease, where so far the dialogue has been, well, we’ll just add more pills, we’ll adjust the levodopa, we’ll add this, we’ll go to a long-acting formulation. At this point you have to say, “No, we’ve added those, or despite those, you’re having OFF episodes.” Let’s pivot that conversation and say, “Let’s plug these gaps.” I had a patient who gave me a clever analogy to this and said, “The road is good, my Parkinson medication works. It’s like I’m driving down a highway, I’m good. When I hit these OFFs, it’s like I hit a rough patch under construction and I have a rough time in that period, and then it passes, and I’m good.” What you’re basically doing with this is, like the analogy my patient gave me, smoothing over those rough patches, where you have a lot of potholes, and that’s how you should look at on-demand therapy in many ways.

Sanjay Iyer, MD: Those are great points, and my patients often say, “Well, I swallowed the pill, and it’s not working. It’s an hour later, an hour and a half later, what’s going on?” I try to let them know that the levodopa has to not only enter your stomach and be broken down, it has to pass into your small intestine where it is absorbed. We’ve all seen the photograph of the intact tablet sitting in the stomach an hour and a half after the patient swallow it, and it hasn’t gotten to where it needs to go. So understanding that, I agree, you can add more and more doses if you want, but if they’re not kicking in; the on-demand therapy, we’re lucky to have it.

Laxman Bahroo, DO: I agree. Many patients expect if they take a pill, it should kick in within 10 minutes. And the reality is under 30 minutes is normal, 30 to 60 is considered dose delay, and 60-plus is considered failure. The same thing today, same person, she came in with dose failure. She had taken her dose at 2:15, and it was about 3:10 or 3:15, and she was not able to walk. I’ll utilize her as a discussion point to see what we did and how we had a conversation. First we discussed the variability, and she’d eaten about 2 or 3 hours before that. It was not food-related as much, but it was just the variability of it. That’s when you want to talk about, maybe we do manage this with something that bypasses the gut to manage these OFF episodes. We’ve got options. We have injectable apomorphine, we have a sublingual formulation of apomorphine. We have an inhaled levodopa. The rationale is, well, I’m having this variability, and now let’s talk about, as we talked about, this pivot, and then let’s discuss where we need to utilize these therapies, and what the outcomes are.

Transcript Edited for Clarity

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