QUANTITATIVE MICRODIALYSIS FOR STUDYING THE IN-VIVO L-DOPA KINETICS IN BLOOD AND SKELETAL-MUSCLE OF THE DOG

In this study the microdialysis technique, using alpha-methyldopa as i nternal standard (IS), is introduced for the in vivo determination of L-DOPA, dopamine (DA), and their metabolites dihydroxyphenylacetic aci d (DOPAC) and 3-O-methyldopa (3-OMD) in blood plasma and skeletal musc le extracellular fluid (ECF), in anaesthetised beagle dogs, after i.v. administration of L-DOPA. In a first calibration experiment, the in v ivo relative losses (RL) of the compounds and the IS were determined. These were lower in skeletal muscle than in blood plasma. K was define d as the ratio of the RL of the IS to the RL of the compound of intere st and was shown to be constant for a certain compound within one tiss ue. However, except for DA, a significant difference was seen in K val ues between blood plasma and skeletal muscle. In a second step, the me thod was validated in blood plasma. The AUC(0-->3) values for the non- protein bound L-DOPA did not differ significantly between the dialysis (141.3 +/- 16.0 nmol.h/ml) and traditional whole blood sampling (145. 3 +/- 18.7 nmol.h/ml), confirming that microdialysis combined with acc urate calibration is a reliable technique for studying the kinetics of drugs in vivo in different tissues.