Abstract
Levodopa uptake from the gastrointestinal tract in patients with Parkinson’s disease (PD) can be affected by delayed gastric emptying (GE). This might lead to fluctuating levodopa levels resulting in increased motor fluctuations. Continuous dopaminergic stimulation (CDS) improves motor fluctuations and could be a result of smoothening in levodopa uptake. In this study we wanted to study the levodopa pharmacokinetics peripherally in PD patients with motor fluctuations and investigate the relation between levodopa uptake and GE and the effect of CDS. PD patients with wearing off (group 1) and on-off syndrome (group 2) were included. Breath tests were performed to evaluate the half time (T1/2) of GE. Concomitantly 1 tablet of Madopark® was given and the levodopa concentrations in blood and subcutaneous (SC) tissue were analyzed for both groups. Group 2 was then given a 10-d continuous intravenous levodopa treatment and the tests were repeated. Higher levels of levodopa in group 1 compared to group 2 in blood (p = 0.014) were seen. The GE was delayed in both group 1 (p < 0.001) and group 2 (p < 0.05) compared to a reference group with healthy volunteers with T1/2 median values 105 and 78 min vs. 72 min. There was no difference in GE between the two PD groups (p = 0.220) or in group 2 before and after infusion period (p = 0.861). CDS resulted in lower levodopa levels in blood (p < 0.001) and SC tissue (p < 0.01). In conclusion, PD patients in early complication phase have a more favourable levodopa uptake than patients later in disease. We found delayed GE in PD patients with motor fluctuations but no obvious relation between GE and levodopa uptake or GE and PD stage. The effect of CDS indicates no effect of CDS on the mechanisms of GE but on the mechanisms of levodopa uptake.
Highlights
IntroductionGiven levodopa is absorbed in the proximal one-third of the small intestine and the competition between levodopa and other large neutral amino acids across the intestinal mucosa is a factor [1] [2]
Levodopa is still the gold standard in the treatment of patients with Parkinson’s disease (PD) but there are several factors affecting the availability of levodopa.Orally given levodopa is absorbed in the proximal one-third of the small intestine and the competition between levodopa and other large neutral amino acids across the intestinal mucosa is a factor [1] [2]
It has been shown that more than 70% of PD patients suffer from impaired gastric motility [4] [5] with symptoms like early satiety, postprandial bloating and nausea and it has been suggested that this is caused by the delay in gastric emptying (GE) that has been shown in PD patients [5]-[13]
Summary
Given levodopa is absorbed in the proximal one-third of the small intestine and the competition between levodopa and other large neutral amino acids across the intestinal mucosa is a factor [1] [2]. Another factor is the gastric emptying (GE) [3]. Delayed GE has been shown to impair the levodopa uptake and is suggested to worsen motor fluctuations [4] [11] [14] [15] [16]. A question is if CDS can result in changes of the GE indicating a postsynaptic dependency of GE
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