Summary
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 halflife 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 (t1/2 α = 0.17 h). The elimination half-life of l-dopa in the controls was higher in muscle (t1/2 β = 1.76 h) than in blood plasma (t1/2 β = 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 3,4-Dihydroxyphenylacetic acid (DOPAC) concentrations in dialysates from blood plasma and muscle showed similar changes in their pharmacokinetic profiles following carbidopa treatment suggesting that their concentrations reflected the formation of these metabolites at other peripheral organs.
Our data support the hypothesis that carbidopa, at least in this experimental setting, exerts a l-dopa sparing effect in skeletal muscle ECF and therefore might play a role in maintaining blood plasma levels of this amino acid.
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Correspondence to: D. Deleu at the above address
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Deleu, D., Sarre, S., Ebinger, G. et al. The effect of carbidopa on the pharmacokinetics and metabolism of intravenously administered levodopa in blood plasma and skeletal muscle. Naunyn-Schmiedeberg's Arch Pharmacol 348, 576–581 (1993). https://doi.org/10.1007/BF00167232
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DOI: https://doi.org/10.1007/BF00167232