L-DOPA biotransformation: correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in Parkinsonian patients.
The objectives of this study were to determine (1) the effects of dose and drug absorption on pathways of biotransformation of L-DOPA in Parkinsonian patients treated with Sinemet, and (2) the extent to which genetically-determined variations in the activities of erythrocyte catechol O-methyltransferase and/or platelet phenol sulfotransferase might be reflected in individual differences in L-DOPA metabolism. In the 19 patients studied, there were negative correlations between dosage or absorption and extent of O-methylation and of sulfation of L-DOPA or its metabolites. Levels of activity for erythrocyte COMT were also reflected in individual variation in the metabolism of L-DOPA. In contrast, differences in platelet phenol sulfotransferase were not reflected in differences in sulfation of L-DOPA or of its metabolites. If such a relationship did exist, it might have been obscured by the effects of high dosage of L-DOPA, effects which might have resulted from a deficiency of the sulfation cosubstrate 3'-phosphoadenosine 5'-phosphosulfate in patients taking higher doses of drug.
Dousa
M K
MK
Department of Physiology, Mayo Clinic/Foundation, Rochester, MN, USA.
Weinshilboum
R M
RM
Muenter
M D
MD
Offord
K P
KP
Decker
P A
PA
Tyce
G M
GM
D000244:Adenosine Diphosphate / Q000378:metabolism; D000368:Aged; D015239:Arylsulfotransferase / Q000378:metabolism*; D001711:Biotransformation; D001792:Blood Platelets / Q000201:enzymology; D002230:Carbidopa / Q000493:pharmacokinetics*; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology*; D012436:S-Adenosylmethionine / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism
D004338:Drug Combinations; D013431:Sulfates; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D000244:Adenosine Diphosphate; D012436:S-Adenosylmethionine; C010840:adenosine 3'-phosphate-5'-phosphate; D002394:Catechol O-Methyltransferase; D015239:Arylsulfotransferase; D002230:Carbidopa