Theeffects oforal protein on theabsorption of intraduodenal levodopa andmotorperformance

suMMARY Fourpatients withlevodopa induced fluctuations inmotorperformance were studied during theconstant intraduodenal infusion oflevodopa. Theresults confirm thatsteady plasma levodopa levels withstable motorcontrol canbeachieved. However, whenpatients weregiven oral protein loads, motorperformance declined despite maintenance ofplasma levodopa levels. These findings suggest that competition forlevodopa carrier mediated transport byaminoacids, ismore important attheblood-brain barrier thanacrossthegutmucosa; thereby possibly limiting the efficacy oflong-term direct intraduodenal administration oflevodopa. Fluctuation ofmotorfunction isusual inlevodopa treated patients withParkinson's disease.' The peripheral pharmacokinetic properties oflevodopa lead tovariable delivery tothecentral nervous system andcontribute tomotoroscillations. Theseinclude effects ofgastrointestinal factors influencing absorption,2 relatively rapidperipheral metabolism of levodopa andcompetition foractive transport across theblood-brain barrier.34 Patients taking orallevodopa frequently remark thatafter a large protein-containing mealtheir medication fails towork. Cotzias wasable toconfirm this observation andadvocated alowprotein diet.5 Delayed orerratic gastric emptying andcompetition between levodopa andlarge neutral aminoacids for gutmucosal carrier systems mayimpair levodopa absorption.6 However, motorfunction isalso adversely affected byoralaminoacidintake when stable plasma levodopa levels aremaintained by intravenous infusion,7 suggesting that competition for transport across theblood-brain barrier also occurs. Thishasalso beendemonstrated byinvivopositron emission tomographic (PET) imaging.8 Inpractice the importance ofthisfactor inpatients receiving conventional oral levodopa medication isdifficult to determine, asplasma levodopa andaminoacid levels maybesimultaneously affected bytheingestion of protein-rich- food.