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

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Abstract

Objectives

Whereas 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.

Methods

Thirty-one patients with PD were enrolled in the study. They were 11 men and 20 women; age, 68.1 ± 7.8 years; disease duration, 4.2 ± 3.8 years; Unified Parkinson's Disease Rating Scale Part 3 Motor Score 18.37 ± 8.60; bowel movement < 3 times a week in 20; all taking 301 mg ± 94 mg/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.

Results

Pharmacokinetic study showed that the plasma levodopa peak was at 2 hours in 42% (13/31 patients) whereas at 1 hour in 58% (18/31 patients), total of 50.7 ± 16.4 min (mean ± standard deviation) in all 31 patients. The gastric emptying study showed that Tmax (13C) > 60 min was more common in patients with a plasma levodopa peak at 2 hours (14/18, 69%) than in those with a plasma levodopa peak at 1 hour (4/13, 22%) (p < 0.05), total of 50.7 ± 16.4 min in all 31 patients.

Conclusion

We 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.

Introduction

Whereas delayed gastric emptying is believed to be a causative factor for producing delayed-on and motor fluctuation in Parkinson's disease (PD) [1], few studies have directly measured levodopa pharmacodynamics and gastric emptying together [2], [3]. In order to determine the relationship, we measured these two parameters in a single PD patients cohort.

Section snippets

Methods

Thirty-one patients who were diagnosed with PD [4] were enrolled in the study. They were 11 men and 20 women; age, 68.1 ± 7.8 years (mean ± standard deviation); disease duration, 4.2 ± 3.8 years; Modified Hoehn and Yahr stage 2.5 ± 0.71; Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 Motor Score 18.37 ± 8.60; bowel movement < 3 times a week (constipation) in 20; all taking 301 mg ± 94 mg/day levodopa [as Menesit tablet [levodopa 100 mg/carbidopa 10 mg] in Japan]. Pharmacokinetic study was performed in

Results

Pharmacokinetic study showed that the plasma levodopa peak was at 2 hours in 42% (13/31 patients) whereas at 1 hour in 58% (18/31 patients), total of 50.7 ± 16.4 min (mean ±  standard deviation) in all 31 patients (Fig. 1). The gastric emptying study showed that Tmax (13C) > 60 min was more common in patients with a plasma levodopa peak at 2 hours (14/18, 69%) than in those with a plasma levodopa peak at 1 hour (4/13, 22%) (p < 0.05) (Fig. 1).

The gastric emptying study also showed that 3 patients showed

Discussion

Previously, Evans et al. [2] measured gastric emptying time by 99mTc-diethyleletriamine-penta-acetic acid gastric scintigraphy and plasma levodopa concentration in 6 PD patients. However, he found no close relationship between these two parameters in his cohort. Dizdar et al. [3] administered the 13C-octanoic acid breath test and plasma levodopa concentration in one PD patient; he found delayed levodopa peak and slow gastric emptying time in this case. In the present study, we found a

Conflict of interest statement

None of the authors have conflict of interest.

Acknowledgments

Author contributions:

Hirokazu Doi has a role in acquisition, analysis and interpretation of data.

Ryuji Sakakibara has a role in study concept and design, acquisition of subjects and/or data, analysis and interpretation of data, and preparation of manuscript.

Mitsutoshi Sato has a role in acquisition of subjects and/or data.

Tohru Masaka has a role in acquisition of subjects and/or data.

Masahiko Kishi has a role in acquisition of subjects and/or data.

Akihiko Tateno has a role in acquisition of

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