Simultaneous monitoring of levodopa, dopamine and their metabolites in skeletal muscle and subcutaneous tissue in different pharmacological conditions using microdialysis.
Microdialysis, in combination with ion-pair reversed-phase liquid chromatography and electrochemical detection is described for the simultaneous determination of levodopa, dopamine, 3-O-methyldopa and 3,4-dihydroxyphenylacetic acid in the extracellular space of skeletal muscle and subcutaneous tissue in vivo in beagle dog. The relative recoveries in vitro for levodopa, dopamine, 3-O-methyldopa and 3,4-dihydroxyphenylacetic acid with a 16 mm probe at a flow rate of 5 microliters min-1 were 29.1, 25.1, 34.7 and 30.1%, respectively. This technique was then applied for three types of pharmacological experiments. In the first experiment L-dopa was administered without carbidopa pretreatment, in the second one, L-dopa was administered following carbidopa pretreatment, and in the last experiment, following pretreatment with both carbidopa and the catechol-O-methyltransferase inhibitor, OR-611. After the administration of levodopa without carbidopa pretreatment, all four compounds could be detected in dialysates from skeletal muscle, whereas dopamine and 3,4-dihydroxyphenylacetic acid were not found in dialysates from 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 method enables the pharmacokinetics and metabolism of levodopa to be studied in subcutaneous tissue and skeletal muscle simultaneously.
Deleu
D
D
Department of Neurology, University Hospital, Brussels, Belgium.
Sarre
S
S
Ebinger
G
G
Michotte
Y
Y
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D002230:Carbidopa / Q000008:administration & dosage / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D004285:Dogs; D004298:Dopamine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D004563:Electrochemistry; D005110:Extracellular Space / Q000378:metabolism; D007275:Injections, Intravenous; D007980:Levodopa / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D008750:Methyldopa / Q000378:metabolism / Q000493:pharmacokinetics*; D009132:Muscles / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D008750:Methyldopa; D002230:Carbidopa; D004298:Dopamine