Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease.

摘要: Abstract Background: When levodopa therapy is used in Parkinson's disease, degradation of the drug peripheral nervous system associated with dyskinesias and motor fluctuations. Much this produced by catechol- O -methyltransferase (COMT), an enzyme involved metabolism catecholamines catechol compounds. Inhibition COMT activity prolongs action reduces fluctuations response. Entacapone a selective inhibitor whose primarily system, little effect central system. Objective: This paper reviews pharmacologic properties clinical usefulness entacapone treatment disease. Methods: Recent studies, abstracts, published English-language literature were identified through searches MEDLINE ® (1966–September 2000), International Pharmaceutical Abstracts (1970–September PharmaProjects (September 2000 version), from Web sites disease conferences held 1996 to September 2000. Relevant human studies provided further information on entacapone. Results: rapidly absorbed, time maximum concentration ∼1 hour. Its plasma elimination half-life 0.4 0.7 hour beta phase 2.4 hours gamma phase, it has 35% absolute bioavailability after oral administration, secondary first-pass clearance. 98% protein bound; thus, not distributed widely tissues almost completely metabolized before excretion (0.1%–0.2% dose unchanged urine). The inhibits erythrocyte-soluble dose-dependent fashion (48% 400-mg dose, 82% 800-mg dose). inhibitory reversible, recovery soluble within 4 8 hours. In levodopa-treated patients who experience fluctuations, trials have demonstrated entacapone's effectiveness increasing "on" (the period during which medications relieve symptoms disease) up 1.2 hours, decreasing "off" increase) 0.9 1.3 producing overall total improvement scores Unified Disease Rating Scale. recommended dosage 200 mg administered orally each levodopa/carbidopa, doses per day. generally well tolerated, most adverse effects attributed levodopa-related dopaminergic effects, including nausea. Conclusions: trials, adjuvant appeared be effective well-tolerated therapeutic strategy response therapy. increased concomitant results greater more sustained levels, constant stimulation brain amelioration parkinsonian symptoms.