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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The effect of carbidopa and entacapone pretreatment on the L-dopa pharmacokinetics and metabolism in blood plasma and skeletal muscle in beagle dog: an in vivo microdialysis study.

The effects of carbidopa and entacapone pretreatment on the pharmacokinetics and metabolism of i.v. administered L-3,4-dihydroxyphenylalanine (L-dopa) have been examined in vivo in blood plasma and skeletal muscle extracellular fluid (ECF), in beagle dog, by microdialysis. Both with or without carbidopa, blood plasma L-dopa levels declined biexponentially after the i.v. administration of L-dopa. In contrast to blood plasma, a monoexponential decline was observed in muscle ECF in both these pharmacological conditions. Pretreatment with carbidopa had no significant effect on the pharmacokinetic parameters of L-dopa in blood plasma, but resulted in an increase in the area under the concentration versus time curve (AUC) and elimination half-life (t1/2) of L-dopa in muscle ECF (0.61 hr), compared with values achieved after L-dopa alone. Carbidopa pretreatment enhanced the accumulation of 3-O-methyldopa (3-OMD) and dopamine (DA) in muscle ECF but decreased that of L-3,4-dihydroxyphenylacetic acid (DOPAC) in both blood plasma and muscle ECF. Entacapone had a pronounced inhibitory effect on the formation of 3-OMD, resulting in a reduction of the AUC for 3-OMD by 98% and 85% in blood plasma and muscle ECF, respectively. Pretreatment with carbidopa plus entacapone enhanced the Tmax of L-dopa in muscle ECF compared with the values achieved after pretreatment with carbidopa alone. In addition, the elimination half-life (2.66 hr) and volume of distribution by area of L-dopa in blood plasma and its AUC and t1/2 in muscle ECF (1.80 hr) were enhanced substantially. No DA was detected, but DOPAC levels were enhanced in both blood plasma and muscle ECF. These results suggested that carbidopa has a L-dopa-sparing effect in skeletal muscle, which is further enhanced by entacapone.[1]


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