Association of CYP2B6 and OPRM1 Genotypes with Methadone Dose Requirements and Serum Concentrations in a Vietnamese Cohorts

To characterize the prevalence of CYP2B6 and OPRM1 gene polymorphisms and evaluate their associations with serum methadone concentrations and dose requirements in Vietnamese patients undergoing methadone maintenance treatment (MMT). This cross-sectional study enrolled 200 patients with opioid dependence from multiple MMT clinics in Ninh Binh, Vietnam, between October 2023 and March 2024. Demographic, clinical, and behavioral data were collected using structured questionnaires. Blood samples were obtained for genotyping CYP2B6 (rs2279343 [785A>G], rs3745274 [516G>T], rs8192709 [64C>T]) and OPRM1 (A118G, rs1799971) using Sanger sequencing. Trough serum methadone concentrations were measured by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multivariable linear regression was performed to identify clinical and genetic factors associated with serum methadone concentrations, the concentration-to-dose ratio (CDR), and maintenance methadone dose. Among 200 participants (99% male, 96.9% Kinh ethnicity), the most common CYP2B6 diplotypes were *1/*4 (33.3%) and *4/*6 (23.7%), with the OPRM1 AG genotype present in 47.5%. Most patients (53.5%) had been on methadone treatment for over 3 years. In multivariable regression, the *1/*6 genotype was independently associated with lower maintenance dose (β = −26.33, 95% CI: −51.97, −0.69). The *2/*6 genotype was significantly associated with lower log serum methadone concentration (β = −2.485, 95% CI: −3.024, −1.947) and lower log CDR (β = −2.595, 95% CI: −3.145, −2.046). Most demographic, behavioral, and OPRM1 genotypes showed no significant associations. Specific CYP2B6 genotypes and SNPs significantly influence methadone pharmacokinetics in Vietnamese patients receiving MMT, although actual daily dose remains the most important determinant of serum levels. These findings highlight the potential role of genotype-guided methadone dosing in optimizing therapy for opioid dependence in Vietnamese populations.