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.
Department of Neurology, University Hospital, Brussels, Belgium.
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D
Deleu
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S
Sarre
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G
Ebinger
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Y
Michotte
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