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Clinical Chemistry 45: 1813-1820, 1999;
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(Clinical Chemistry. 1999;45:1813-1820.)
© 1999 American Association for Clinical Chemistry, Inc.

Articles

Human Pharmacokinetics of L-3,4-Dihydroxyphenylalanine Studied with Microdialysis

Nil Dizdar1,a, Anita Kullman1, Björn Norlander2, Jan-Edvin Olsson3 and Bertil Kgedal1

Departments of
1 Clinical Chemistry,
2 Clinical Pharmacology, and
3 Neurology, University Hospital, S-581 85 Linköping, Sweden.
a Author for correspondence. Fax 46-13-223240; e-mail Nil.Dizdar{at}lio.se

Background: Intravenous and subcutaneous microdialysis was performed to compare the free concentrations and pharmacokinetics of L-3,4-dihyroxyphenylalanine (L-dopa) in blood and tissue in healthy subjects and in patients with Parkinson disease.

Methods: Nine healthy volunteers and 10 patients with Parkinson disease, stage 1.5–2 according to the Hoehn-Yahr rating scale, took part of the study. In the patient group subcutaneous microdialysis and ordinary blood sampling were performed, whereas in the control group intravenous microdialysis was also performed. Microdialysis samples were collected in fractions of 15 min. The first two fractions were collected for analysis of basal concentrations. A blood sample was also taken. The patients were then given one tablet of Madopar® (100 mg of L-dopa and 25 mg of benserazide), and the microdialysis was continued for another 210 min. Blood samples were obtained at 30-min intervals.

Results: The serum samples gave a significantly higher mean area under the curve (AUC; 491 ± 139 µmol · min/L) than that for intravenous dialysates (235 ± 55.3 µmol · min/L), suggesting a protein binding of 50%. The L-dopa concentrations from the subcutaneous dialysates matched those from the intravenous dialysates, indicating rapid distribution of L-dopa to the tissues.

Conclusions: Parkinsonian patients in early stages of the disease have a pharmacokinetic pattern of free L-dopa similar to that of healthy subjects. Comparison of AUCs from microdialysis with ordinary serum analysis revealed data indicating significant protein binding. Microdialysis is a suitable and easily applied tool in pharmacokinetic studies.






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Copyright © 1999 by the American Association for Clinical Chemistry.