title: L-DOPA biotransformation: correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in Parkinsonian patients.
abstract: 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.
authors.affiliation: Department of Physiology, Mayo Clinic/Foundation, Rochester, MN, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Dousa
authors.forename: R M
authors.initials: RM
authors.lastname: Weinshilboum
authors.forename: M D
authors.initials: MD
authors.lastname: Muenter
authors.forename: K P
authors.initials: KP
authors.lastname: Offord
authors.forename: P A
authors.initials: PA
authors.lastname: Decker
authors.forename: G M
authors.initials: GM
authors.lastname: Tyce
mesh_terms: 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
chemical_list: 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