Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets.
Continuous duodenal infusion of carbidopa/levodopa has been shown to control motor fluctuations in advanced Parkinson's disease (PD). The authors compared the pharmacokinetics of levodopa and 3-O-methyldopa in patients with advanced PD after administration of an oral sustained-release levodopa preparation and after continuous intestinal levodopa infusion with a new formulation as a gel suspension. A randomized crossover trial was carried out in 12 patients. Carbidopa/levodopa was administered as an oral sustained-release tablet and by nasoduodenal continuous infusion for 3-week periods for each treatment. Plasma levodopa concentrations and motor performance were evaluated every 30 minutes during 3 test days of each treatment period. The average intraindividual coefficient of variation for the plasma levodopa concentrations after oral therapy was 34% and was significantly lower (14%, p < 0.01) during continuous infusion. Hourly video evaluations showed a significant increase in ON time during infusion and a significant decrease in OFF time and dyskinesia. Continuous intraduodenal delivery of a new carbidopa/levodopa formulation offers a means for markedly improved control of motor fluctuations in late stages of PD.
Nyholm
Dag
D
Department of Neuroscience, Neurology, Uppsala University, Sweden. dag.nyholm@neurologi.uu.se
Askmark
Håkan
H
Gomes-Trolin
Cecilia
C
Knutson
Tina
T
Lennernäs
Hans
H
Nyström
Christer
C
Aquilonius
Sten-Magnus
SM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002230:Carbidopa / Q000008:administration & dosage; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004386:Duodenum; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D007980:Levodopa / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D007980:Levodopa; D002230:Carbidopa