Pharmacokinetics and effects of levodopa in advanced Parkinson's disease

Five patients with severe Parkinson's disease were characterized with respect to their pharmacokinetic and pharmacodynamic responses to levodopa given: orally, intravenously (three different infusion rates) and intraduodenally. The best therapeutic infusion rate in the intravenous study was used for the intraduodenal infusion of levodopa. A lag time between plasma concentration and effect following oral administration was seen in three of the five patients and this disequilibrium was estimated as the rate constant Ke0 using model-independent analysis. The plasma concentration-effect relationship was similar for the three modes of administration and in all patients the therapeutic plasma concentration for full mobility was greater than 4-5 micrograms.ml-1. The disequilibrium half-life for development of effect after oral administration was calculated to be about 30 min. The patients remained clinically stable during the period of the intraduodenal infusion.