Monitoring of L-dopa concentrations in Parkinson's disease

Although it is the treatment of choice in the management of idiopathic Parkinson's disease, l-DOPA (LD) shows a decline in its efficacy after years of prolonged use, with the appearance of severe motor disturbances. These complications have been interpreted on pharmacokinetic and pharmacodynamic grounds. The main pharmacokinetic reason is considered to be the decreased capacity in LD activation to dopamine along with reduction of its storage ability in the nigrostriatal terminals, as a result of disease progression. At this stage the LD action in the extrapyramidal system is thought to be closely dependent on its synaptic cleft concentrations, being directly related to those in the systemic circulation and to the events possibly perturbing them. Therapeutic drug monitoring might be useful to explain these modifications in relation to the clinical effect and even to possible problems in transport competition and so to define the LD dosage regimen. Recently LD threshold concentrations have been suggested by means of sophisticated pharmacokinetic-pharmacodynamic approaches. Unfortunately they do not correspond to real therapeutic ranges but to levels in a hypothetical effect compartment in no steady-state conditions, due to remarkable LD fluctuations. However they are considered helpful to the functional state interpretation of the nigrostriatal system.