CLINICAL DRUG-MONITORING BY MICRODIALYSIS - APPLICATION TO LEVODOPA THERAPY IN PARKINSONS-DISEASE

1 We describe the first application of microdialysis to monitor the ph armacokinetics of a drug in the blood of man. 2 The aims of the study were to ascertain patient acceptability and tolerability of a new micr odialysis probe and to assess its accuracy in determining the pharmaco kinetics of levodopa and its principal plasma metabolite 3-O-methyldop a (3-OMD). 3 Eight patients with parkinsonism on chronic levodopa ther apy were investigated. 4 After an overnight fast, a flexible microdial ysis probe, perfused with isotonic saline, was inserted into a forearm vein and a blood sampling cannula was inserted in a forearm vein of t he other arm. After ingestion of a levodopa preparation (Madopar Dispe rsible(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 pro files were similar to those of plasma, and levodopa and 3-OMD concentr ations exhibited significant (P<0.001) correlation with those observed in the corresponding plasma samples. 6 The mean (+/-s.d.) blood dialy sate 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 th e probe was excellent, and all eight patients found it preferable to c onventional blood sampling. 8 Microdialysis of blood is less invasive than frequent intermittent direct blood sampling, and can readily be u sed to continuously monitor levodopa pharmacokinetics. In a clinical s etting, a combination of drug monitoring by this technique together wi th clinical evaluation of motor function can be used to optimize levod opa treatment in patients with Parkinson's disease.