title: Variation in the dopaminergic response during the day in Parkinson disease.
abstract: OBJECTIVE
  In many parkinsonian patients with fluctuating disease the early morning levodopa dose is more effective than the following dose on the same day. In this study we investigated whether the poor responsiveness to the early afternoon dose of levodopa depends only on peripheral and central levodopa pharmacokinetics or also on pharmacodynamic factors.
  
  
  METHODS
  Ten parkinsonian patients experiencing postprandial drug-resistant off periods received two boluses of apomorphine by subcutaneous injection at 8 am and 3 pm on two nonconsecutive days. On day 2, therapy was stopped at 11 am. For each bolus we determined time to on, duration of the on state, magnitude of benefit, and levodopa and apomorphine plasma levels at baseline and immediately after patients reached the on state.
  
  
  RESULTS
  The mean duration of on phases was significantly shorter and the apomorphine plasma level needed to reach the on state was significantly higher in the afternoon than in the morning (P<0.01 by paired t test).
  
  
  CONCLUSIONS
  This study suggest that there is a change in responsiveness to dopaminergic stimulation during the day. The less effective dopaminergic response in afternoon depends on pharmacodynamic factors and not only on peripheral and central levodopa pharmacokinetic.
authors.affiliation: Casa Di Cura Villa Margherita Arcugnano (VI), Roma, Italy. AlessandraMonge@libero.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Monge
authors.forename: Fabio
authors.initials: F
authors.lastname: Viselli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Stocchi
authors.forename: Luca
authors.initials: L
authors.lastname: Barbato
authors.forename: Andrea
authors.initials: A
authors.lastname: Bolner
authors.forename: Nicola
authors.initials: N
authors.lastname: Modugno
authors.forename: Michele
authors.initials: M
authors.lastname: Paradiso
authors.forename: Stefano
authors.initials: S
authors.lastname: Ruggieri
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Nordera
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001058:Apomorphine; D002940:Circadian Rhythm; D018491:Dopamine Agonists; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D007980:Levodopa; D001058:Apomorphine