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Effect of entacapone, a COMT inhibitor, on the pharmacokinetics of levodopa and on cardiovascular responses in patients with Parkinson's disease.

Abstract：

:In an open, randomised, cross-over study we investigated the effect of a single 200 mg oral dose of entacapone, a novel catechol-O-methyltransferase (COMT) inhibitor, on the pharmacokinetics and metabolism of levodopa/carbidopa, and on the cardiovascular responses (blood pressure and pulse rate variation to standard stimuli) in eight parkinsonian patients. Entacapone significantly increased the mean area under the plasma concentration curve (AUC) of levodopa by 46%, from 3620 to 5280 h.ng.ml-1 and prolonged its elimination half-life (t1/2el) from 1.5 h to 2.0 h. The mean AUC of 3,4-dihydroxyphenylacetic acid (DOPAC), the monoamine oxidase-dependent metabolite of levodopa, was significantly increased from 122 to 343 h.micrograms.ml-1 by entacapone. A small decrease in the AUC of homovanillic acid (HVA), the COMT dependent metabolite of levodopa, was observed (from 455 to 303 h.ng.ml-1). Entacapone also decreased the excretion of HVA but not that of 3-methoxytyramine in the urine. Cardiovascular autonomic responses to sympathetic and parasympathetic stimuli were not changed by entacapone. We conclude that a single dose of entacapone moderately increases the AUC and prolongs the t1/2el of levodopa in man and that that does not affect cardiovascular autonomic regulation.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Myllylä VV,Sotaniemi KA,Illi A,Suominen K,Keränen T

doi

10.1007/BF00315512

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

419-23

issue

5

eissn

0031-6970

issn

1432-1041

journal_volume

45

pub_type

临床试验,杂志文章,随机对照试验

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