Variation in the dopaminergic response during the day in Parkinson disease.
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.
Monge
Alessandra
A
Casa Di Cura Villa Margherita Arcugnano (VI), Roma, Italy. AlessandraMonge@libero.it
Viselli
Fabio
F
Stocchi
Fabrizio
F
Barbato
Luca
L
Bolner
Andrea
A
Modugno
Nicola
N
Paradiso
Michele
M
Ruggieri
Stefano
S
Nordera
Gianpietro
G
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
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D007980:Levodopa; D001058:Apomorphine