Quantitative microdialysis for studying the in vivo L-DOPA kinetics in blood and skeletal muscle of the dog.
In this study the microdialysis technique, using alpha-methyldopa as internal standard (IS), is introduced for the in vivo determination of L-DOPA, dopamine (DA), and their metabolites dihydroxyphenylacetic acid (DOPAC) and 3-O-methyldopa (3-OMD) in blood plasma and skeletal muscle extracellular fluid (ECF), in anaesthetised beagle dogs, after i.v. administration of L-DOPA. In a first calibration experiment, the in vivo relative losses (RL) of the compounds and the IS were determined. These were lower in skeletal muscle than in blood plasma. K was defined as the ratio of the RL of the IS to the RL of the compound of interest and was shown to be constant for a certain compound within one tissue. However, except for DA, a significant difference was seen in K values between blood plasma and skeletal muscle. In a second step, the method was validated in blood plasma. The AUC0-->3 values for the non-protein bound L-DOPA did not differ significantly between the dialysis (141.3 +/- 16.0 nmol.h/ml) and traditional whole blood sampling (145.3 +/- 18.7 nmol.h/ml), confirming that microdialysis combined with accurate calibration is a reliable technique for studying the kinetics of drugs in vivo in different tissues.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002138:Calibration; D003956:Dialysis / Q000379:methods; D004285:Dogs; D004298:Dopamine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007980:Levodopa / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D008750:Methyldopa / Q000032:analysis; D008832:Microchemistry / Q000379:methods; D018482:Muscle, Skeletal / Q000378:metabolism*; D011485:Protein Binding; D012015:Reference Standards; D015203:Reproducibility of Results; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics
D001798:Blood Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D014443:Tyrosine; D007980:Levodopa; D008750:Methyldopa; C008404:3-methoxytyrosine; D004298:Dopamine