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), dialysate was collected over 5 or 10 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.
O'Connell
M T
MT
Pharmacology and Therapeutics Unit, National Hospital for Neurology and Neurosurgery, London, UK.
Tison
F
F
Quinn
N P
NP
Patsalos
P N
PN
D000978:Antiparkinson Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D016903:Drug Monitoring; D006207:Half-Life; D006801:Humans; D007980:Levodopa / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D017551:Microdialysis / Q000009:adverse effects / Q000379:methods*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism
D000978:Antiparkinson Agents; D014443:Tyrosine; D007980:Levodopa; C008404:3-methoxytyrosine