Monitoring of L-dopa concentrations in Parkinson's disease

Although it is the treatment of choice in the management of idiopathic Park inson's disease, L-DOPA (LD) shows a decline in its efficacy after years of prolonged use, with the appearance of severe motor disturbances. These com plications have been interpreted on pharmacokinetic and pharmacodynamic gro unds. The main pharmacokinetic reason is considered to be the decreased cap acity in LD activation to dopamine along with reduction of its storage abil ity in the nigrostriatal terminals, as a result of disease progression. At this stage the LD action in the extrapyramidal system is thought to be clos ely 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 modifica tions in relation to the clinical effect and even to possible problems in t ransport competition and so to define the LD dosage regimen. Recently LD th reshold concentrations have been suggested by means of sophisticated pharma cokinetic-pharmacodynamic approaches. Unfortunately they do not correspond to real therapeutic ranges bur to levels in a hypothetical effect compartme nt in no steady-state conditions, due to remarkable LD fluctuations. Howeve r they are considered helpful to the functional state interpretation of the nigrostriatal system. (C) 2001 Academic Press.