Dousa M K, Weinshilboum R M, Muenter M D, Offord K P, Decker P A, Tyce G M
Department of Physiology, Mayo Clinic/Foundation, Rochester, MN, USA.
J Neural Transm (Vienna). 2003 Aug;110(8):899-910. doi: 10.1007/s00702-003-0001-2.
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.
（1）剂量和药物吸收对接受息宁治疗的帕金森病患者中左旋多巴生物转化途径的影响；（2）红细胞儿茶酚-O-甲基转移酶和/或血小板酚磺基转移酶活性的基因决定变异在左旋多巴代谢个体差异中可能得到反映的程度。在所研究的19名患者中，左旋多巴或其代谢产物的O-甲基化程度和硫酸化程度与剂量或吸收之间呈负相关。红细胞儿茶酚-O-甲基转移酶的活性水平也反映在左旋多巴代谢的个体差异中。相比之下，血小板酚磺基转移酶的差异并未反映在左旋多巴或其代谢产物的硫酸化差异中。如果确实存在这样的关系，那么它可能已被高剂量左旋多巴的影响所掩盖，这种影响可能是由于服用较高剂量药物的患者中硫酸化共底物3'-磷酸腺苷5'-磷酸硫酸酯缺乏所致。
