Pharmacokinetics of L-dopa in plasma and extracellular fluid of striatum in common marmosets.
L-3, 4-Dihydroxyphenylalanine (L-dopa) has been widely used for the treatment of Parkinson's disease (PD), but its pharmacokinetics in the striatum have hardly been investigated, especially in primates. In this study, we examined the concentration of L-dopa in plasma and in the extracellular fluid (ECF) of the striatum in common marmosets using microdialysis and high-performance liquid chromatography (HPLC) with electrochemical detection. With a clinically therapeutic dosage of L-dopa/benserazide (20/5 mg/kg, p.o.), the t(max) of L-dopa was 30 min in plasma and 60-90 min in ECF of striatum. Mean C(max) was 20.3 microM in plasma and 442.9 nM in ECF of striatum, which is about 2.2% of that in plasma. The L-dopa concentration in ECF is much lower than those previously applied during in vivo studies for L-dopa toxicity.
Zhang
Jie
J
Department of Clinical Pharmacology and Therapeutics, School of Medicine, Ehime University, Shigenobu, Ehime 791-0295, Japan.
Qu
Fu-rong
FR
Nakatsuka
Akiko
A
Nomura
Takuo
T
Nagai
Masahiro
M
Nomoto
Masahiro
M
D000818:Animals; D002144:Callithrix; D003342:Corpus Striatum / Q000098:blood supply / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects; D005260:Female; D007980:Levodopa / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D017551:Microdialysis; D013997:Time Factors
D007980:Levodopa