SIMULTANEOUS MONITORING OF LEVODOPA, DOPAMINE AND THEIR METABOLITES IN SKELETAL-MUSCLE AND SUBCUTANEOUS TISSUE IN DIFFERENT PHARMACOLOGICALCONDITIONS USING MICRODIALYSIS
D. Deleu et al., SIMULTANEOUS MONITORING OF LEVODOPA, DOPAMINE AND THEIR METABOLITES IN SKELETAL-MUSCLE AND SUBCUTANEOUS TISSUE IN DIFFERENT PHARMACOLOGICALCONDITIONS USING MICRODIALYSIS, Journal of pharmaceutical and biomedical analysis, 11(7), 1993, pp. 577-585
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.