title: The pharmacokinetics of intravenous and oral levodopa in patients with Parkinson's disease who exhibit on-off fluctuations.
abstract: We have studied the clinical effects and pharmacokinetics of levodopa infusions and oral therapy in seven patients with Parkinson's disease. They all showed on-off fluctuations whilst receiving long-term treatment with levodopa in combination with a peripheral decarboxylase inhibitor. Intravenous infusion at a constant rate for up to 16 h resulted in a smoother clinical response, and maintained plasma levodopa concentrations within narrower limits compared with conventional oral therapy. Following infusion rates of 32-80 mg h-1 (0.5-1.3 mg kg-1 h-1) the plasma concentration associated with optimum therapeutic response lay between 0.3 and 1.6 mg l-1. There was considerable variation in the oral absorption and elimination of levodopa, both within and between subjects. The concentration of 3-OMe dopa in plasma hardly increased during each day's levodopa therapy. In all cases levels were greater than the maximum concentrations of levodopa, sometimes by as much as a factor of 10. In contrast to most previous reports on the pharmacokinetics of levodopa, the data presented here are consistent with a two-compartment kinetic model. It is not known whether the difference in pharmacokinetics is due to chronic therapy or whether it is specific to those patients who show on-off phenomena, but such changes might be related in some way to the development of fluctuations in clinical response.
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D007980:Levodopa / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D011897:Random Allocation; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D014443:Tyrosine; D007980:Levodopa; D002262:Carboxy-Lyases; C008404:3-methoxytyrosine