Plasma levodopa peak delay and impaired gastric emptying in Parkinson's disease.
OBJECTIVE
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 (13)C-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 T(max) ((13)C)>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.


CONCLUSIONS
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.
Pharmaceutical Unit, Sakura Medical Center, Toho University, Sakura, Japan.
Hirokazu
H
Doi
Ryuji
R
Sakakibara
Mitsutoshi
M
Sato
Tohru
T
Masaka
Masahiko
M
Kishi
Akihiko
A
Tateno
Fuyuki
F
Tateno
Yohei
Y
Tsuyusaki
Osamu
O
Takahashi
D000368:Aged; D000978:Antiparkinson Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001944:Breath Tests; D005260:Female; D005746:Gastric Emptying / Q000502:physiology*; D018589:Gastroparesis / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
D000978:Antiparkinson Agents; D007980:Levodopa