The catechol-O-methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson's disease

Piccini, Paola; Brooks, David J.; Korpela, K.; Pavese, Nicola; Karlsson, MariAnne; Gordin, A.

doi:10.1136/jnnp.68.5.589

Cited by 65 publications

(27 citation statements)

References 31 publications

(10 reference statements)

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“…selegiline and rasagiline) [23], catechol O-methyl-transferase (COMT) inhibitors (i.e. entacapone and tolcapone) [24,25] and dopamine receptor agonists (i.e. ergot D 2 R agonists:…”

Section: Neurobiology Of Parkinson's Diseasementioning

confidence: 99%

An Update on Adenosine A2A Receptors as Drug Target in Parkinson's Disease

Vallano¹,

Fernández-Dueñas²,

Pedrós³

et al. 2011

CNSNDDT

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“…selegiline and rasagiline) [23], catechol O-methyl-transferase (COMT) inhibitors (i.e. entacapone and tolcapone) [24,25] and dopamine receptor agonists (i.e. ergot D 2 R agonists:…”

Section: Neurobiology Of Parkinson's Diseasementioning

confidence: 99%

An Update on Adenosine A2A Receptors as Drug Target in Parkinson's Disease

Vallano¹,

Fernández-Dueñas²,

Pedrós³

et al. 2011

CNSNDDT

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“…A typical treatment is to use a COMT inhibitor to prolong the elimination half-life of L-dopa in Parkinson's disease (Piccini et al, 2000), and the nitrocatechol COMT inhibitors, entacapone and tolcapone, are widely used in clinical therapy. A further point of concern is to discover completely new COMT inhibitors without a nitrocatechol structure, which possibly is associated with some side effects (Männistö and Kaakkola, 1999).…”

Section: Role Of Comt In Disposition Of Luteolin In Ratsmentioning

confidence: 99%

Role of Catechol-O-Methyltransferase in the Disposition of Luteolin in Rats

Chen¹,

Chen²,

Pan³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Luteolin is mainly metabolized by phase II enzymes in animals and humans with glucuronidation and sulfation as the two known metabolic pathways. Although methylation of luteolin was reported previously, the structure of the methylated metabolites and the enzymes involved in the process have not been clarified. In our study, two methylated metabolites, M1 (chrysoeriol) and M2 (diosmetin), were identified in the urine after intravenous administration of luteolin to rats, and the data suggested that the methylation was mediated by catechol-O-methyltransferase (COMT). When luteolin was coadministered with a specific COMT inhibitor, entacapone, the formation of M1 and M2 was significantly reduced, whereas the plasma concentration of luteolin increased. Methylation of luteolin was also studied in vitro using rat tissue homogenates. The apparent kinetic parameters associated with the formation of M1 and M2 in vitro were estimated, and regioselectivity of methylation of luteolin was observed. In the in vitro experiment, there was a preference for the formation of M2 over M1. In contrast, accumulation of M1 was preferred in vivo in both rat plasma and urine after an intravenous dose of luteolin. In conclusion, COMT played a crucial role in the disposition of luteolin in rats. Our results indicated that the methylation pathway in rats was significantly reduced when luteolin was coadministered with a specific COMT inhibitor. Therefore, COMT-associated drug-drug interactions need be considered in the future in luteolin clinical trials because the plasma concentrations and related therapeutic effects may be altered in vivo in the presence of a COMT inhibitor.

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“…Several randomised, placebo controlled, double-blind, adjunct entacapone studies have been reported in PD patients with motor fluctuations [6,51,55,59]. Their duration was usually 6 months.…”

Section: Phase III Clinical Efficacy Trials In Pd Patients With Motormentioning

confidence: 99%

“…The safety of entacapone has been extensively investigated using data from five phase III controlled studies [6,37,51,55,69] and their long-term extensions [29,56,74] (Table 2) as well as placebo controlled [12] and uncontrolled studies [11,13] and wide practical experience.…”

Section: Safety Of Entacaponementioning

confidence: 99%