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.
Original language | English (US) |
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Pages (from-to) | 899-910 |
Number of pages | 12 |
Journal | Journal of Neural Transmission |
Volume | 110 |
Issue number | 8 |
DOIs | |
State | Published - Aug 1 2003 |
Keywords
- 3′-phosphoadenosine 5′-phosphosulfate
- L-DOPA absorption
- L-DOPA:biotransformation
- L-DOPA:pharmacogenomics
- S-adenosyl-L-methionine
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Psychiatry and Mental health
- Biological Psychiatry