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Disease progression, drug action and Parkinson’s disease: Why time cannot be ignored

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Abbreviations

α:

Slope of linear disease status curve

Ce:

Effect compartment concentration

CeSS :

Steady state effect site concentration at the start of each levodopa infusion derived from endogenous dopamine and previous exogenous levodopa administration

C0pnss:

Non-steady state levodopa concentration in plasma

C0snss:

Non-steady state component of the slow equilibration effect compartment

D max :

Maximum levodopa induced response above baseline

Dvtpk:

Duration of uniform diurnal input.

EC50:

Concentration at which 50% of maximum response is produced.

E max :

Maximum tapping rates that a drug can produce.

Hill:

Hill coefficient which determine the steepness of the concentration–response curve.

RDiurnal :

Ratio of diurnal input to constant input of endogenous dopamine

Rsynd:

Rate of levodopa equivalent dopamine synthesis in the dopa synthesis effect compartment during the diurnal input period

S0:

Baseline status

Teqd:

Equilibration half-life of the dopa synthesis effect compartment

Teqf:

Equilibration half-life of the fast equilibration effect compartment

Teqs:

Equilibration half-life of the slow equilibration effect compartment

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Acknowledgements

Dr. Nutt is supported by NIH RO1-NS21062 and Veterans Administration Parkinson’s Disease Research, Education and Clinical Center (PADRECC).

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Authors and Affiliations

  1. Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand

    Nick Holford

  2. Department of Neurology, Oregon Health and Science University, Portland, OR, USA

    John G. Nutt

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Correspondence to Nick Holford.

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Holford, N., Nutt, J.G. Disease progression, drug action and Parkinson’s disease: Why time cannot be ignored. Eur J Clin Pharmacol 64, 207–216 (2008). https://doi.org/10.1007/s00228-007-0427-9

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