In vivo pharmacokinetics of levodopa and 3-O-methyldopa in muscle. A microdialysis study.

In the present study in vivo microdialysis sampling coupled to high-performance liquid chromatography with electrochemical detection, was used to study the pharmacokinetics of levodopa and 3-O-methyldopa in skeletal muscle in dog, after intravenous administration of levodopa. For comparison, the pharmacokinetic parameters of both compounds were simultaneously determined in plasma using blood collection. Muscle microdialysis samples and blood were continuously collected for 4 h after the administration of levodopa (25 mg/kg). Pharmacokinetic profiles of levodopa in plasma and muscle were different. The mean Tmax value of levodopa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC0----inf for levodopa in plasma was nearly 18-fold higher in plasma than in muscle. The 3-O-methyldopa concentration increased very rapidly after the administration of levodopa, to reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC0----4 for 3-O-methyldopa was 3.6-fold higher in plasma than in muscle. The ratio levodopa/3-O-methyldopa, reflecting the metabolic rate of levodopa, was 3.5 times higher in plasma than in muscle, at the peak value of levodopa, and then rapidly declined to values lower than 1, one hour after administration of the drug. We compared our results with literature data from postmortem studies done in rat experiments. We concluded that levodopa is not accumulating in muscle as such, but is converted to 3-O-methyldopa probably before leaving the plasma compartment.