title: The effect of carbidopa on the pharmacokinetics and metabolism of intravenously administered levodopa in blood plasma and skeletal muscle.
abstract: The effect of carbidopa on the pharmacokinetics and metabolism of levodopa (L-dopa) in blood plasma and skeletal muscle extracellular fluid (ECF) has been studied by repeated measurements in one beagle dog. The administration of a single dose of L-dopa (25 mg/kg i.v.) without carbidopa pretreatment (controls) resulted in an increase in the concentrations of L-dopa and 3-O-methyldopa (3-OMD) in blood plasma and skeletal muscle ECF dialysates. This effect was clearly potentiated for L-dopa in blood plasma (186% increase in AUC) and 3-OMD in skeletal muscle dialysates (108% increase in AUC) after pretreatment with carbidopa (100 mg/day). In addition, carbidopa prolonged the half-life of the elimination of L-dopa in blood plasma by 48% and in skeletal muscle ECF by 66% but did not influence its blood plasma distribution half-life (t 1/2 alpha = 0.17 h). The elimination half-life of L-dopa in the controls was higher in muscle (t 1/2 beta = 1.76 h) than in blood plasma (t 1/2 beta = 0.50 h). Carbidopa pretreatment resulted in a relatively small increase (29%) in the L-dopa content of skeletal muscle ECF as indicated by the AUC. The accumulation of 3-OMD in muscle dialysates, in contrast to that in plasma, was significantly enhanced after the administration of L-dopa following treatment with carbidopa. In the control experiments, dopamine (DA) was detectable only in the dialysates from muscle ECF.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Neurology, University Hospital, Vrije Universiteit, Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Deleu
authors.forename: S
authors.initials: S
authors.lastname: Sarre
authors.forename: G
authors.initials: G
authors.lastname: Ebinger
authors.forename: Y
authors.initials: Y
authors.lastname: Michotte
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000097:blood / Q000378:metabolism; D000818:Animals; D002230:Carbidopa / Q000494:pharmacology*; D004285:Dogs; D004298:Dopamine / Q000097:blood / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006207:Half-Life; D007275:Injections, Intravenous; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D014443:Tyrosine; D007980:Levodopa; D002230:Carbidopa; C008404:3-methoxytyrosine; D004298:Dopamine