Simultaneous in vivo microdialysis in plasma and skeletal muscle: a study of the pharmacokinetic properties of levodopa by noncompartmental analysis.
This in vivo study compared the pharmacokinetics of intravenously (iv) administered levodopa (L-dopa) in plasma and skeletal muscle. For this purpose, a single iv dose of L-dopa (25 mg/kg) was given to an anesthetized beagle dog, and L-dopa as well as its O-methyl metabolite, 3-O-methyldopa (3-OMD), were monitored in plasma and skeletal muscle simultaneously by microdialysis. The plasma and muscle dialysates were continuously collected during a 3-h period after the iv administration of the drug. The pharmacokinetic variables were then compared in both tissues with noncompartmental modeling. The mean maximum concentration (Cmax) for L-dopa in plasma was 173.10 +/- 9.85 ng/mL, whereas in skeletal muscle extracellular fluid, it was 14.56 +/- 2.27 ng/mL. The area under the curve of concentration versus time from time zero to infinity (AUC0- > inf) values for L-dopa were 20 times higher in plasma compared with muscle. The difference in half-life between the two tissues probably indicated the large contribution of the distribution phase in either or both tissues over the 3-h time interval. Interestingly enough, the AUC0- > 3h values for 3-OMD were within the same range in both tissues. These data demonstrated that over a period of 3 h, no distribution equilibrium for L-dopa was reached over the two tissues. The very low L-dopa/3-OMD ratios suggested that, in contrast to L-dopa, 3-OMD is accumulating in skeletal muscle. Whether these findings have any implication for the therapeutic response to L-dopa in Parkinson's disease remains to be determined.
Deleu
D
D
Department of Neurology, University Hospital A.Z.-V.U.B., Vrije Universiteit Brussel, Belgium.
Sarre
S
S
Michotte
Y
Y
Ebinger
G
G
D000818:Animals; D004285:Dogs; D007980:Levodopa / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis; D009132:Muscles / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics
D014443:Tyrosine; D007980:Levodopa; C008404:3-methoxytyrosine