Past Issues
Correlation between Cytochrome P450 2D6 Genotype and Methadone
Concentration-to-dose Ratio
Tzu-Yun Wang, Hui Hua Chang, Wei-Ming Ke, Chen-Hsi Chou,Lan-Ting Lee, Yen Kuang Yang, Ru-Band Lu, Po See Chen
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 TaqMan® 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.
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 TaqMan® 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.
| Key Word | ABCB1, pharmacokinetics, CYP 3A4, drug interaction |
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