Levodopa infusion combined with entacapone or tolcapone in Parkinson disease: a pilot trial

European Journal of Neurology, 04/19/2012

According to this small, short–term pilot study, oral catechol–O–methyltransferase inhibitors administered in 5–h intervals may be useful in cases where levodopa/carbidopa intestinal gel dose reduction is wanted. Stability of plasma levodopa levels is not significantly altered, and off–time is not increased when decreasing the levodopa/carbidopa intestinal gel dose by 20%. Rather, the dose should probably be decreased more than 20%, especially under tolcapone co–treatment, to avoid increased dyskinesias with time.


  • A short-term, randomized, partly blinded, crossover, investigator-initiated clinical trial was performed, with levodopa/carbidopa intestinal gel combined with oral entacapone and tolcapone on two different days in 10 patients.
  • The primary outcome measure was difference in coefficient of variation of levodopa in plasma between levodopa/carbidopa, levodopa/carbidopa/entacapone, and levodopa/carbidopa/tolcapone.
  • The secondary outcome measures other pharmacokinetic variables, patient-reported outcome, and blinded analysis of motor performance.


  • Variation of plasma levodopa concentrations did not differ significantly between the treatments.
  • The treatments did not differ regarding motor performance.
  • Levodopa concentrations were significantly higher using tolcapone.
  • Concentrations of the metabolite 3-O-methyldopa decreased gradually during catechol-O-methyltransferase inhibition.

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