Therapeutic drug monitoring in Parkinson’s disease

A patient-tailored therapy of the heterogeneous, neuropsychiatric disorder entity Parkinson's disease (PD) aims to improve dopamine sensitive motor symptoms and associated non-motor features. Subgroups of PD, disease progress and concomitant disorders as well as ageing processes in general, compliance issues, safety and tolerability of the applied drug combinations may influence intake scenarios and dosing regimen and thus the quality of patient care. Therefore, a repeated, individual adaptation of dopamine substituting compounds is required throughout the disease course. Therapeutic drug monitoring (TDM) of dopamine substituting drugs will optimize the quality of drug applications for patients with PD. We suggest plasma determination especially of levodopa, amantadine and dopamine agonists as an essential step. Repeated assessments within standardised protocols in chronic levodopa/dopa decarboxylase inhibitor treated patients will allow monitoring of the levodopa plasma fluctuation index as a potential risk factor for the onset of motor complications in the long term. These measurements may also support the understanding of only partially levodopa responsive PD related syndromes. To date this phenomenon of missing adequate levodopa response has not yet been fully explored in terms of dysfunction of gastrointestinal absorption or blood brain barrier transport of biogenic amines. Measurements of blood levels of dopamine agonists, monoamine oxidase B inhibitors, istradephylline and amantadine are also needed. Outcomes of TDM analyses may serve as disease progression marker complemented by still to be developed future computing procedures on the central need for dopamine supplementation. They will substitute the currently applied calculations of levodopa equivalents as marker of disease progression.