MOTOR FLUCTUATIONS DURING CONTINUOUS LEVODOPA INFUSIONS IN PATIENTS WITH PARKINSONS-DISEASE

The cause of motor fluctuations occurring during constant-rate levodop a infusions is unknown. We examined whether known pharmacokinetic fact ors could explain the fluctuations and looked for clues to pharmacodyn amic causes. Eleven subjects with stage III-V Parkinson's disease (PD) and a fluctuating response to levodopa underwent constant-rate infusi ons for 36-110 h. Levodopa, 3-O-methyldopa (3-OMD), and plasma large n eutral amino acids (LNAAs) were measured at 2- to 6-h intervals and PD was monitored hourly from 07:00 to 22:00 h with tapping speed. Ten su bjects had motor fluctuations during the infusions. Zero to 68% of the variability of tapping speed could be explained by variation in plasm a LNAA concentrations in individual subjects. Fluctuations occurred mo re commonly later in the day, which may be related to the tendency for LNAAs to increase during the day. Motor fluctuations were not associa ted with minor variations in levodopa or 3-OMD concentrations. Fluctua tions during constant infusions were more marked in patients using lar ger daily doses of oral levodopa; severity of PD did not predict fluct uations during the infusions. There was no trend for fluctuations or d yskinesia to decrease or increase during several days of constant-rate levodopa infusion. A portion of motor fluctuations occurring during c onstant levodopa infusions can be explained by peripheral pharmacokine tic mechanisms. Fluctuations are more prominent in subjects who have t aken larger daily doses of levodopa, implicating pharmacodynamic facto rs as well.