P450 2D6細胞色素基因型與美沙冬血中濃度對劑量比例的相關性

Correlation between Cytochrome P450 2D6 Genotype and Methadone Concentration-to-dose Ratio

目的：美沙冬是一個被用來治療鴉片成癮的合成鴉片類藥品，其療效與副作用和其血中 濃度有關。然而濃度對劑量比例有的個別差異，不論是身體或基因因素都會顯著影響接受 美沙冬維持治療個案的體重校正後的濃度對劑量比例。本研究目的為調查接受美沙冬維持治 療後，基因造成的美沙冬代謝與體重校正後的濃度對劑量比例間的關係。方法：美沙冬血 中濃度由HPLC 測得。CYP2D6*10 (rs1065852)，ABCB1C3435T (rs1045642) 和ABCB1G2677T (rs2032582) 基因的基因型不同由 TaqManR SNP genotyping assays 測得。結果：CYP2D6*10 基 因的多型性和體重校正後的濃度對劑量比例有顯著相關 (p < 0.01)，而此比例與美沙冬治療 個案的副作用有顯著相關 (p < 0.01)。結論：比起CYP2D 代謝調控不佳者，調控較佳者有較 低的體重校正後的濃度對劑量比例，然而是否此調控會影響美沙冬維持治療療效仍需要研究。

Objectives: Methadone is a synthetic opioid used to treat opioid dependence. The therapeutic and side effects are well-noted to be correlated with its blood concentration. But the concentration-to-dose ratio (CDR) is highly varied among individuals. Both physiological and genetic factors that have effects on the weightadjusted CDR in subjects are under methadone maintenance therapy (MMT) in Taiwan. In the current study, we intended to study whether variations of genes associated with methadone metabolism are correlated with the weight-adjusted CDR in patients receiving MTT. Methods: We measured the blood concentration of methadone (CMTD) with high-performance liquid chromatography, and genotyped CYP2D6*10 (rs1065852), ABCB1C3435T (rs1045642) and ABCB1G2677T (rs2032582) variations with TaqManR SNP genotyping assays. Results: Results showed that the variation of the CYP2D6*10 gene polymorphisms had a signifi - cant effect on the weight-adjusted CDR (p < 0.01), which was signifi cantly associated with the side effects in subjects receiving MTT (p < 0.05). Conclusion: The study results indicated that CYP2D6 extensive metabolizers had lower weightadjusted CDR than that of the poor metabolizers. Whether the variation is also correlated the outcome of the MMT, merits further investigation.