Nonlinear pharmacodynamics of levodopa through Parkinson's disease progression.

摘要: The effect of levodopa in alleviating the symptoms Parkinson’s disease is altered a highly nonlinear manner as progresses. This can be attributed to different compensation mechanisms taking place basal ganglia where dopaminergic neurons are progressively lost. alteration complicates optimization drug regimen. present work aims at investigating dynamics and its therapy through mechanistic mathematical modeling. Using holistic approach, pharmacokinetic model was combined dopamine neurocomputational ganglia. influence neuronal death on these also integrated. this model, we were able investigate relationships between plasma concentration, brain response motor task. Variations concentrations for doses studied. Finally, investigated narrowing therapeutic index with progression result nonlinearities. In conclusion, various consequences treatment studied by developing an integrative model. paves way toward individualization dosing sensor based information, parameters could fitted individual data propose optimal regimens.