Effect of COMT inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients

John Nutt, Obeso, Reichmann, Olanow, Lieberman, Koller, Fahn, Gordin, Dingemanse, Brooks, ttman Gu ttman

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Catechol-O-methyl transferase (COMT) is one of the principal levodopa-metabolizing enzymes, particularly when aromatic amino acid decarboxylase (AAAD) is partially inhibited by carbidopa or benserazide. This paper examines the pharmacology of COMT inhibitors such as tolcapone and entacapone, and considers the effects of these drugs on the pharmacolinetics of levodopa. Both agents extend the elimination half-life and plasma area under the curve of levodopa without affecting the maximal plasma concentration of levodopa (Cmax) or the time until an oral dose of levodopa reaches its peak plasma concentration (Tmax). Clinically, these pharmacokinetic effects permit a reduction in the levodopa dose, an increase in 'on' time and a decrease in 'off' time in fluctuating PD patients. Motor benefits can also be seen in stable PD patients. COMT inhibitors are thus an alternative to increasing levodopa doses or adding dopamine agonists to reduce 'off' time and enhance motor function in fluctuating PD patients.

Original languageEnglish (US)
JournalNeurology
Volume55
Issue number11 SUPPL. 4
StatePublished - Dec 12 2000

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Guaiacol
Levodopa
Transferases
Pharmacokinetics
Benserazide
Aromatic-L-Amino-Acid Decarboxylases
Carbidopa
Dopamine Agonists
Area Under Curve
Half-Life
Pharmacology
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nutt, J., Obeso, Reichmann, Olanow, Lieberman, Koller, ... Gu ttman, T. (2000). Effect of COMT inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Neurology, 55(11 SUPPL. 4).

Effect of COMT inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. / Nutt, John; Obeso; Reichmann; Olanow; Lieberman; Koller; Fahn; Gordin; Dingemanse; Brooks; Gu ttman, ttman.

In: Neurology, Vol. 55, No. 11 SUPPL. 4, 12.12.2000.

Research output: Contribution to journalArticle

Nutt, J, Obeso, Reichmann, Olanow, Lieberman, Koller, Fahn, Gordin, Dingemanse, Brooks & Gu ttman, T 2000, 'Effect of COMT inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients', Neurology, vol. 55, no. 11 SUPPL. 4.
Nutt J, Obeso, Reichmann, Olanow, Lieberman, Koller et al. Effect of COMT inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Neurology. 2000 Dec 12;55(11 SUPPL. 4).
Nutt, John ; Obeso ; Reichmann ; Olanow ; Lieberman ; Koller ; Fahn ; Gordin ; Dingemanse ; Brooks ; Gu ttman, ttman. / Effect of COMT inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. In: Neurology. 2000 ; Vol. 55, No. 11 SUPPL. 4.
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