SIMULTANEOUS MONITORING OF LEVODOPA, DOPAMINE AND THEIR METABOLITES IN SKELETAL-MUSCLE AND SUBCUTANEOUS TISSUE IN DIFFERENT PHARMACOLOGICALCONDITIONS USING MICRODIALYSIS

Microdialysis, in combination with ion-pair reversed-phase liquid chro matography and electrochemical detection is described for the simultan eous determination of levodopa, dopamine, 3-O-methyldopa and 3,4-dihyd roxyphenylacetic acid in the extracellular space of skeletal muscle an d subcutaneous tissue in vivo in beagle dog. The relative recoveries i n vitro for levodopa, dopamine, 3-O-methyldopa and 3,4-dihydroxyphenyl acetic acid with a 16 mm probe at a flow rate of 5 mul min-1 were 29.1 , 25.1, 34.7 and 30. 1 %, respectively. This technique was then applie d for three types of pharmacological experiments. In the first experim ent L-dopa was administered without carbidopa pretreatment, in the sec ond one, L-dopa was administered following carbidopa pretreatment, and in the last experiment, following pretreatment with both carbidopa an d the catechol-O-methyltransferase inhibitor, OR-611. After the admini stration of levodopa without carbidopa pretreatment, all four compound s could be detected in dialysates from skeletal muscle, whereas dopami ne and 3,4-dihydroxyphenylacetic acid were not found in dialysates fro m subcutaneous tissue. After the administration of levodopa following carbidopa pretreatment and following pretreatment with both carbidopa and OR-611 all compounds could be measured except for dopamine. This m ethod enables the pharmacokinetics and metabolism of levodopa to be st udied in subcutaneous tissue and skeletal muscle simultaneously.