Clinical drug monitoring by microdialysis: Application to levodopa therapy in Parkinson's disease

1 We describe the first application of microdialysis to monitor the pharmacokinetics of a drug in the blood of man. 2 The aims of the study were to ascertain patient acceptability and tolerability of a new microdialysis probe and to assess its accuracy in determining the pharmacokinetics of levodopa and its principal plasma metabolite 3-O-methyldopa (3-OMD). 3 Eight patients with parkinsonism on chronic levodopa therapy were investigated. 4 After an overnight fast, a flexible microdialysis probe, perfused with isotonic saline, was inserted into a forearm vein and a blood sampling cannula was inserted in a forearm vein of the other arm. After ingestion of a levodopa preparation (Madopar Dispersible(R)), dialysate was collected over 5 or IO min periods and blood samples were taken every 15 or 30 min for 2-6 h. 5 Dialysate drug profiles were similar to those of plasma, and levodopa and 3-OMD concentrations exhibited significant (P<0.001) correlation with those observed in the corresponding plasma samples. 6 The mean (+/-s.d.) blood dialysate concentrations for levodopa and 3-OMD were 36.1 +/- 9.2% and 43.4 +/- 8.4% respectively of the plasma content. 7 The tolerability of the probe was excellent, and all eight patients found it preferable to conventional blood sampling. 8 Microdialysis of blood is less invasive than frequent intermittent direct blood sampling, and can readily be used to continuously monitor levodopa pharmacokinetics. In a clinical setting, a combination of drug monitoring by this technique together with clinical evaluation of motor function can be used to optimize levodopa treatment in patients with Parkinson's disease.