PMID: 9818851: Entacapone enhances response to levodopa in PD

[janet paterson <janet313@xxxxxxxxxxx>]

Entacapone enhances the response to levodopa in parkinsonian patients with
motor fluctuations. Nomecomt Study Group.

OBJECTIVE: To study the effect and safety of entacapone as an adjunct to 
levodopa treatment in patients with PD with wearing-off motor fluctuations.

BACKGROUND: Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that 
has been shown to increase the area under the concentration-time curve of 
plasma levodopa by decreasing its systemic elimination, thereby promoting and 
improving therapeutic response to it.

METHODS: A total of 171 parkinsonian patients with wearing-off-type motor 
fluctuations participated in a 6-month randomized, placebo-controlled, 
double-blind, parallel-group study.

The extent of therapeutic response was elicited in the first hand with home 
diary recordings of "on" and "off" times by the patient and with Unified 
Parkinson's Disease Rating Scale scoring by the examiner.

The patients took either 200 mg entacapone or identical placebos concomitantly 
with each daily levodopa dose (four to 10 times a day).

RESULTS: Patients' home diaries indicated that entacapone increased the mean 
(+/- SD) "on" time significantly (9.3 +/- 2.2 to 10.7 +/- 2.2 hours; p < 0.01) 
and correspondingly decreased the "off" time significantly (5.3 +/- 2.2 to 4.2 
+/- 2.2 hours; p < 0.001).

The average benefit derived from a daily levodopa dose as related by the 
patients was increased significantly (p < 0.01).

The daily levodopa dose was reduced significantly in the entacapone group, the 
difference between the groups being 102 mg (p < 0.01).

The entacapone-derived increase in the benefit from levodopa was lost almost 
completely following its withdrawal.

Entacapone was well tolerated.

Dopaminergic adverse events, which increased, were ameliorated by reducing the 
levodopa dose.

Diarrhea was the most common nondopaminergic adverse event.

CONCLUSIONS: Long-term entacapone treatment effectively prolonged the 
beneficial response to levodopa in parkinsonian patients with the wearing-off 
phenomenon.

The improvement occurred irrespective of the reduction of the levodopa dose.


Neurology 1998 Nov;51(5):1309-14
Rinne UK, Larsen JP, Siden A, Worm-Petersen J
Department of Neurology, Turku University Hospital, Finland.
PMID: 9818851, UI: 99034160

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janet paterson
52 now / 41 dx / 37 onset
613 256 8340 po box 171 almonte ontario canada K0A 1A0
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<janet313@xxxxxxxxxxx>