Plasma levodopa peak delay and impaired gastric emptying in Parkinson's disease

Abstract

ObjectivesWhereas delayed gastric emptying is believed to be a causative factor for producing delayed-on and motor fluctuation in Parkinson's disease (PD), few studies have directly measured levodopa pharmacodynamics and gastric emptying together. In order to determine the relationship, we measured these two parameters in a single PD patients cohort. MethodsThirty-one patients with PD were enrolled in the study. They were 11 men and 20 women; age, 68.1±7.8years; disease duration, 4.2±3.8years; Unified Parkinson's Disease Rating Scale Part 3 Motor Score 18.37±8.60; bowel movement <3 times a week in 20; all taking 301mg±94mg/day levodopa/carbidopa. All patients underwent levodopa pharmacokinetic study and the gastric emptying study using 13C-octanoic acid expiration breath test. Statistical analysis was performed by Student's t-test and Mann–Whitney's U test. ResultsPharmacokinetic study showed that the plasma levodopa peak was at 2hours in 42% (13/31 patients) whereas at 1hour in 58% (18/31 patients), total of 50.7±16.4min (mean±standard deviation) in all 31 patients. The gastric emptying study showed that Tmax (13C)>60min was more common in patients with a plasma levodopa peak at 2hours (14/18, 69%) than in those with a plasma levodopa peak at 1hour (4/13, 22%) (p<0.05), total of 50.7±16.4min in all 31 patients. ConclusionWe found a significant relationship between levodopa pharmacokinetics and gastric emptying in PD patients, suggesting that delayed gastric emptying is a causative factor for producing delayed-on in PD. Therefore, studies of improved gastric emptying in order to ameliorate delayed-on in PD are warranted.