Methadone has a wide pharmacokinetic interindividual variability, resulting in unpredicted treatment response. Pharmacogenomic biomarkers seem promising for personalized methadone maintenance treatment. The evidence supports the use of ABCB1 single-nucleotide polymorphism (SNP) 1236C>T with genotypes C/T or C/C (Jewish) and haplotypes AGCTT carrier, AGCGC heterozygote, or non-carrier (Caucasian), which have a predicted lower methadone dose requirement. In contrast, ABCB1 SNP 1236C>T with genotype T/T (Jewish); haplotypes AGCGC homozygote, AGCTT non-carrier (Caucasian), and ABCB1 3435C>T variant carrier; and haplotypes CGT, TTC, and TGT (Han Chinese) have a predicted higher methadone dose. For methadone plasma levels, ABCB1 diplotype non-CGC/TTT (Malay) predicted lower, and diplotype CGC/TTT (Malay), 3435C>T allelic carrier, haplotypes (CGT, TTC, TGT) (Han Chinese) predicted higher methadone levels. In terms of metabolism biomarkers, a lower methadone requirement was related to carriers of CYP2B6 genotypes *4(G/G) and *9(T/T) among Jewish patients, CYP2B6*9 genotype (T/T) and haplotypes (TA/TG); and CYP2C19 (*2/*2,*2/*3, and *3/*3; Han Chinese). Higher methadone dose was observed in CYP2C19*1 allelic carriers (Han Chinese) and CYP2D6 ultrarapid metabolizer (Caucasian). Lower methadone levels were reported in CYP2B6 SNPs, haplotypes TTT, and AGATAA (Han Chinese), CYP2C19 genotype *1/*1 (Han Chinese), allelic carrier *1xN (Caucasian), and CYP3A4 genotype *1/*1 (Caucasian). Carriers of CYP2B6 genotype *6/*6 (Caucasian), CYP2B6 haplotypes ATGCAG and ATGCTG (Han Chinese), and CYP3A4 genotype *1/*1B (Caucasian) had predicted higher methadone plasma levels. Specific pharmacokinetics biomarkers have potential uses for personalized methadone treatment in specific populations.

中文翻译：

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个性化美沙酮维持治疗的药物基因组学生物标志物：机制及其潜在用途。

美沙酮具有广泛的药代动力学个体差异，导致无法预测的治疗反应。药物基因组学生物标志物似乎有望用于个性化美沙酮维持治疗。证据支持使用具有基因型 C/T 或 C/C（犹太）和单倍型 AGCTT 携带者、AGCGC 杂合子或非携带者（白种人）的 ABCB1 单核苷酸多态性 (SNP) 1236C>T美沙酮剂量要求。相比之下，ABCB1 SNP 1236C>T，基因型为T/T（犹太人）；单倍型 AGCGC 纯合子、AGCTT 非携带者（白种人）和 ABCB1 3435C>T 变异携带者；和单倍型 CGT、TTC 和 TGT（汉族）预测的美沙酮剂量更高。对于美沙酮血浆水平，ABCB1 双倍型非 CGC/TTT（马来人）预测较低，双倍型 CGC/TTT（马来人），3435C>T 等位基因携带者，单倍型（CGT、TTC、TGT）（汉族）预测美沙酮水平较高。在代谢生物标志物方面，较低的美沙酮需求与犹太患者中 CYP2B6 基因型 *4(G/G) 和 *9(T/T)、CYP2B6*9 基因型 (T/T) 和单倍型 (TA/ TG); 和 CYP2C19（*2/*2、*2/*3 和 *3/*3；汉族）。在 CYP2C19*1 等位基因携带者（汉族）和 CYP2D6 超快代谢者（白种人）中观察到更高的美沙酮剂量。在 CYP2B6 SNP、单倍型 TTT 和 AGATAA（汉族）、CYP2C19 基因型 *1/*1（汉族）、等位基因携带者 *1xN（白种人）和 CYP3A4 基因型 *1/*1（白种人）中报告了较低的美沙酮水平. 携带 CYP2B6 基因型 *6/*6（白种人）、CYP2B6 单倍型 ATGCAG 和 ATGCTG（汉族）以及 CYP3A4 基因型 *1/*1B（白种人）的携带者预测美沙酮血浆水平较高。