NEUROLOGY 1994;44:913
© 1994 American Academy of Neurology
Effect of peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients
J. G. Nutt, MD,
W. R. Woodward, PhD,
R. M. Beckner, BA,
C. K. Stone,
K. Berggren, BA,
J. H. Carter, MN,
S. T. Gancher, MD,
J. P. Hammerstad, MD and
A. Gordin, MD
Departments of Neurology, School of Medicine (Drs. Nutt, Woodward, Gancher, and Hammerstad and R.M. Beckner, C.K. Stone, K. Berggren, and J.H. Carter)
Departments of Pharmacology (Dr. Nutt)
Departments of Biochemistry and Molecular Biology, School of Medicine (Dr. Woodward, R.M. Beckner, and K. Berggren)
Department of Adult Health and Illness, School of Nursing, Oregon Health Sciences University, Portland, (J.H. Carter)
Department of Orion-Farmos Pharmaceuticals Research Center, Espoo, Finland. (Dr. Gordin)
Article abstract –Catechol-O-methyltransferase (COMT) metabolizes a portion of administered levodopa and thus makes it unavailable for conversion to dopamine in the brain. In an open-label trial, we examined the effects of entacapone, a peripheral inhibitor of COMT, administered acutely or for 8 weeks, on the pharmacokinetics and pharmacodynamics of levodopa in 15 parkinsonian subjects with a fluctuating response to levodopa. Acutely and chronically administered entacapone similarly decreased the plasma elimination of orally and intravenously administered levodopa. Absorption of levodopa was minimally affected. During chronic entacapone treatment, daily levodopa dosages were reduced by 27% yet mean plasma levodopa concentrations were increased by 23%. Plasma 3-O-methyldopa concentrations were decreased by 60%. Entacapone increased the duration of action of single doses of levodopa by a mean of 56%. The percent of the day "on" after 8 weeks of entacapone treatment was 77%; it dropped to 44% upon withdrawal of entacapone. We conclude that inhibition of COMT by entacapone increases the plasma half-life of levodopa and augments the antiparkinsonian effects of single and repeated doses of levodopa.
Address correspondence and reprint requests to Dr. J.G. Nutt, Department of Neurology, L-226, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098.
Supported in part by NIH grants NS21062 and RR00334 and a grant from Orion-Farmos Pharmaceuticals.
Received July 27, 1993. Accepted for publication in final form November 1, 1993.
This article has been cited by other articles:
|
|
|
|
 
C. W. Olanow, M. B. Stern, and K. Sethi
The scientific and clinical basis for the treatment of Parkinson disease (2009)
Neurology,
May 26, 2009;
72(21_Supplement_4):
S1 - S136.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Stocchi, L. Vacca, P. Grassini, M. F. De Pandis, G. Battaglia, C. Cattaneo, and R. G. Fariello
Symptom relief in Parkinson disease by safinamide: Biochemical and clinical evidence of efficacy beyond MAO-B inhibition.
Neurology,
October 10, 2006;
67(7 Suppl 2):
S24 - S29.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A H V Schapira
Present and future drug treatment for Parkinson's disease
J. Neurol. Neurosurg. Psychiatry,
November 1, 2005;
76(11):
1472 - 1478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. de la Fuente-Fernandez, M. Schulzer, E. Mak, D. B. Calne, and A. J. Stoessl
Presynaptic mechanisms of motor fluctuations in Parkinson's disease: a probabilistic model
Brain,
April 1, 2004;
127(4):
888 - 899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. M. Swope
Rapid treatment of "wearing off" in Parkinson's disease
Neurology,
March 23, 2004;
62(6_suppl_4):
S27 - S31.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
Parkinson Study Group
The safety and tolerability of a mixed lineage kinase inhibitor (CEP-1347) in PD
Neurology,
January 27, 2004;
62(2):
330 - 332.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. C. Koller and W. Tse
Unmet medical needs in Parkinson's disease
Neurology,
January 13, 2004;
62(90011):
S1 - 8.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
W. Poewe
The role of COMT inhibition in the treatment of Parkinson's disease
Neurology,
January 13, 2004;
62(90011):
S31 - 38.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. J. Brooks
Safety and tolerability of COMT inhibitors
Neurology,
January 13, 2004;
62(90011):
S39 - 46.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. A. Hauser
Levodopa/carbidopa/entacapone (Stalevo)
Neurology,
January 13, 2004;
62(90011):
S64 - 71.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. W. Olanow and F. Stocchi
COMT inhibitors in Parkinson's disease: Can they prevent and/or reverse levodopa-induced motor complications?
Neurology,
January 13, 2004;
62(90011):
S72 - 81.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D J Brooks and H Sagar
Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson's disease: a randomised, placebo controlled, double blind, six month study
J. Neurol. Neurosurg. Psychiatry,
August 1, 2003;
74(8):
1071 - 1079.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kompoliti, C. H. Adler, R. Raman, J. H. Pincus, M. T. Leibowitz, J. J. Ferry, L. Blasucci, J. N. Caviness, S. Leurgans, W. M. Chase, et al.
Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics
Neurology,
May 14, 2002;
58(9):
1418 - 1422.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Lee, H. S. Kim, E. K. Cho, J. H. Lim, and J. O. Rinne
COMT genotype and effectiveness of entacapone in patients with fluctuating Parkinson's disease
Neurology,
February 26, 2002;
58(4):
564 - 567.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. W. Olanow, R. L. Watts, and W. C. Koller
An algorithm (decision tree) for the management of Parkinson's disease (2001):: Treatment
Neurology,
June 12, 2001;
56(suppl_5):
S1 - S88.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A Munchau and K P Bhatia
Pharmacological treatment of Parkinson's disease
Postgrad. Med. J.,
October 1, 2000;
76(900):
602 - 610.
[Full Text]
|
|
|
|
|
|
|
P. Piccini, D. J Brooks, K. Korpela, N. Pavese, M. Karlsson, and A. Gordin
The catechol-O-methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson's disease
J. Neurol. Neurosurg. Psychiatry,
May 1, 2000;
68(5):
589 - 594.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
P. T. Mannisto and S. Kaakkola
Catechol-O-methyltransferase (COMT): Biochemistry, Molecular Biology, Pharmacology, and Clinical Efficacy of the New Selective COMT Inhibitors
Pharmacol. Rev.,
December 1, 1999;
51(4):
593 - 628.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H Baas, A G Beiske, J Ghika, M Jackson, W H Oertel, W Poewe, and G Ransmayr
Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients
J. Neurol. Neurosurg. Psychiatry,
October 1, 1997;
63(4):
421 - 428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Quinn
Fortnightly Review: Drug treatment of Parkinson's disease
BMJ,
March 4, 1995;
310(6979):
575 - 579.
[Abstract]
[Full Text]
|
|
|
|
