OPRM1 and CYP3A4 association with methadone dose in Iranian patients undergoing methadone maintenance therapy

Akbari, Abolfazl; Kheradmand, Ali; Sina, Marzie; Ahmadiani, Abolhassan; Asadi, Sareh

doi:10.1080/10550887.2021.1886566

Cited by 3 publications

(8 citation statements)

References 25 publications

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“…Some studies have found that the patients with rs1799971 G allele require a higher methadone dose 33,39 . However, other investigations did not find the association of this polymorphism with MMT response or dose 32,35–38 …”

Section: Discussionmentioning

confidence: 99%

“…The OPRM1 rs1799971 has emerged as one of the most promising candidates to function as a genetic predictor of the MMT response. Several reports have evaluated the association of rs1799971 with methadone treatment outcome or dose, but the results have been contradictory 10,32–39 . Some studies have found that the patients with rs1799971 G allele require a higher methadone dose 33,39 .…”

Section: Discussionmentioning

confidence: 99%

“…33,39 However, other investigations did not find the association of this polymorphism with MMT response or dose. 32,[35][36][37][38] We attempted to find the evidence of rs1799971 as a predictor of the response to MMT. However, we did not find significant evidence that rs1799971 plays a critical role in MMT in our samples or in meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Individuals with the rs1799971 variation may have differences in receptor activities, resulting in individual variability in the clinical response to methadone. Some research studies explored the correlation of OPRM1 rs1799971 with MMT response or dose, but a definitive conclusion remains elusive 32–38 . For instance, the results are different in different populations.…”

Section: Introductionmentioning

confidence: 99%

“…Some research studies explored the correlation of OPRM1 rs1799971 with MMT response or dose, but a definitive conclusion remains elusive. [32][33][34][35][36][37][38] For instance, the results are different in different populations. Wang et al 39 found an association between allele G and higher methadone dosage in a Chinese Han cohort (366 cases), whereas Levran et al 10 reported no association of rs1799971 with methadone dose in a Caucasian ethnic group (227 patients).…”

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confidence: 99%

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Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response

Xie

Zhuang

et al. 2022

Clinical Laboratory Analysis

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Heroin dependence is an ongoing public health issue worldwide, and methadone maintenance treatment (MMT) is currently an effective substitution therapy for patients with heroin addiction. Methadone, as a synthetic agonist of the mu opioid receptor, can reduce illicit opiate use and improve social rehabilitation. 1,2 There is an obvious difference in individual response to methadone due to large interindividual variability in its pharmacokinetics and pharmacodynamics. [3][4][5][6][7] Optimal personalized medicine for each patient is vital for successful MMT. 8,9 Genetic factors are related to the diversity of individuals in responding to MMT. [10][11][12] Several articles reported that numerous variations in multiple genes are related to modification of the individual MMT response. [13][14][15] Single nucleotide polymorphisms (SNPs) of several genes are significant associations with MMT, such as the genes

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response

Xie

Zhuang

et al. 2022

Clinical Laboratory Analysis

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Association of the OPRM1 variant rs1799971 (A118G) and clinical manifestations in tramadol poisoned patients: a cross-sectional study

Ershad,

Shafiee Dolat Abadi,

Ebrahimian

et al. 2024

Clinical Toxicology

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CYP2B6 and ABCB1 genotypes predict methadone plasma exposure among patients on maintenance therapy against opioid addictions in Tanzania

Mugusi,

Mnkugwe,

Sanga

et al. 2024

Brit J Clinical Pharma

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AimsMethadone maintenance therapy (MMT) exhibits significant variability in pharmacokinetics and clinical response, partly due to genetic variations. However, data from sub‐Saharan African populations are lacking. We examined plasma methadone variability and pharmacogenetic influences among opioid‐addicted Tanzanian patients.MethodsPatients attending MMT clinics (n = 119) in Tanzania were genotyped for common functional variants of the CYP3A4, CYP3A5, CYP2A6, CYP2B6, CYP2C19, CYP2D6, ABCB1, UGT2B7 and SLCO1B1 genotypes. Trough plasma concentrations of total methadone, S‐methadone (S‐MTD) and R‐methadone (R‐MTD), with their respective metabolites, 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (EDDP), were quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The methadone‐to‐EDDP metabolic ratio (MMR) was used to categorize the phenotype.ResultsThe proportions of MMR‐predicted ultrarapid, extensive, intermediate and slow methadone metabolizer phenotypes were 2.5%, 58.2%, 23.7% and 15.6%, respectively. CYP2B6 genotype significantly correlated with S‐methadone (P = .006), total methadone (P = .03), and dose‐normalized methadone plasma concentrations (P = .001). Metabolic ratios of R‐methadone (R‐MTD/R‐EDDP), S‐methadone (S‐MTD/S‐EDDP), and total methadone (MMR) were significantly higher among patients homozygous for defective variants (*6 or *18) than heterozygous or CYP2B6*1/*1 genotypes (P < .001). The metabolic ratio for S‐MTD and total methadone was significantly higher among ABCB1c.3435T/T than in the C/C genotype. No significant effect of CYP2D6, CYP2C19, CYP3A4, CYP3A5, CYP2A6, UGT2B7 and SLCO1B1 genotypes on S‐methadone, R‐methadone, or total methadone was observed.ConclusionsApproximately one in six opioid‐addicted Tanzanian patients are methadone slow metabolizers, influenced by genetic factors. Both the CYP2B6 and ABCB1 genotypes are strong predictors of methadone metabolic capacity and plasma exposure. Further investigation is needed to determine their predictive value for methadone treatment outcomes and to develop genotype‐based dosing algorithms for safe and effective therapy.

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OPRM1 and CYP3A4 association with methadone dose in Iranian patients undergoing methadone maintenance therapy

Cited by 3 publications

References 25 publications

Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response

Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response

Association of the OPRM1 variant rs1799971 (A118G) and clinical manifestations in tramadol poisoned patients: a cross-sectional study

CYP2B6 and ABCB1 genotypes predict methadone plasma exposure among patients on maintenance therapy against opioid addictions in Tanzania

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