Moving toward Personalized Medicine in the Methadone Maintenance Treatment Program: A Pilot Study on the Evaluation of Treatment Responses in Taiwan

Lee, Hsin Ya; Li, Jih Heng; Sheu, Yuh Ling; Tang, Hsin Pei; Chang, Wei Chiao; Tang, Tze Chun; Yeh, Yi Chun; Wang, Shing Yaw; Liu, Ray H.

doi:10.1155/2013/741403

Cited by 18 publications

(17 citation statements)

References 51 publications

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“…Pharmacokinetic status of family members such as CYP2B6 and CYP3A4 have been associated with plasma concentrations of methadone but connections to dose requirements have been more equivocal 7, 11–14 . Genotypes at ABCB1 , a gene encoding a transmembrane efflux pump, have also been linked to methadone serum levels and dose 15–17 . As with the CYP genes, a number of studies have failed to replicate the ABCB1 associations with dose (reviewed in 7 ).…”

Section: Introductionmentioning

confidence: 99%

Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African–Americans with opioid use disorder

et al. 2018

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Many patients with opioid use disorder do not have successful outcomes during treatment but the underlying reasons are not well understood. An OPRD1 variant (rs678849) was previously associated with methadone and buprenorphine efficacy in African-Americans with opioid use disorder. The objective of this study was to determine if the effect of rs678849 on opioid use disorder treatment outcome could be replicated in an independent population. Participants were recruited from African-American patients who had participated in previous studies of methadone or buprenorphine treatment at the outpatient treatment research clinic of the NIDA Intramural Research Program in Baltimore, MD, USA between 2000 and 2017. Rs678849 was genotyped retrospectively and genotypes were compared to urine drug screen results from the previous studies for opioids other than the one prescribed for treatment. Genotypes were available for 24 methadone patients and 55 buprenorphine patients. After controlling for demographics, the effect of rs678849 genotype was significant in the buprenorphine treatment group (RR = 1.69, 95% confidence interval (CI) 1.59–1.79, p = 0.021). Buprenorphine patients with the C/C genotype were more likely to have opioid-positive drug screens than individuals with the C/T or T/T genotypes, replicating the original pharmacogenetic finding. The effect of genotype was not significant in the methadone group (p = 0.087). Thus, genotype at rs678849 is associated with buprenorphine efficacy in African-Americans being treated for opioid use disorder. This replication suggests that rs678849 genotype may be a valuable pharmacogenetic marker for deciding which opioid use disorder medication to prescribe in this population.

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Section: Introductionmentioning

confidence: 99%

Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African–Americans with opioid use disorder

et al. 2018

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“…In their 2018 review, Fonseca and Torrens highlighted the influence of CYP2B6 , and to some extent CYP2D6 and CYP2C19 , genetic variability on methadone pharmacokinetics . Three studies described in that review reported that the CYP2B6 gene had no influence on the methadone response.…”

Section: Discussionmentioning

confidence: 99%

Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study

Victorri-Vigneau

Verstuyft

Bouquié

et al. 2019

Brit J Clinical Pharma

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Aims: Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6-G516T and CYP2D6 genetic polymorphisms on pharmacokinetic and clinical parameters in patients receiving methadone maintenance treatment. Methods: Opioid PhArmacoLogy (OPAL) was a clinical survey of the sociodemographic characteristics, history and consequences of pathology associated with methadone maintenance treatment response and current addictive comorbidities. A subgroup of 72 methadone patients was genotyped. Results: When comparing the three CYP2B6 genotype groups, the methadone (R)and (S)-methadone enantiomer concentrations/doses (concentrations relative to doses) were different (P = .029, P = .0019). The CYP2D6 phenotypes did not seem to be relevant with regard to methadone levels. On multivariate analysis, neither the CYP2B6 genotype nor the CYP2D6 phenotype explained the (R)-methadone concentration/dose values (P = .92; P = .86); the (S)-methadone concentration/dose values (P = .052; P = .95 [although there was a difference between the TT group and GT and GG groups {P = .019}]); or opiate cessation (P = .12; P = .90).Conclusion: The genotyping of CYP2B6 G516T could be an interesting tool to explore methadone intervariability.

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“…A Swiss study of 14 MMT subjects found the ABCB1 genotypes 3435 TT, CT, and CC resulted in 3, 23 and 33% increases in (R)-methadone concentration/dose ratios following administration of P-gp substrate quetiapine, respectively (158). Carriers of the variant ABCB1 3435C>T were found to require higher doses of methadone than non-carriers among a population of Han Chinese patients (157), and a pilot study of 178 Taiwanese patients in a MMT program found the ABCB1 2677T allele had positive effects on methadone plasma concentration (159).…”

Section: Methadonementioning

confidence: 99%

“…Some clinical studies have suggested there is a likely relationship (155)(156)(157)(158)(159), while others have suggested there is likely not (161)(162)(163)165), and still others propose that ABCB1 polymorphisms are only one of a number of interacting pharmacogenetic determinants influencing methadone pharmacokinetics (160). Despite extensive research, there remains considerable controversy over the functional consequences of various ABCB1 polymorphisms (222)(223)(224)(225).…”

Section: Methadonementioning

confidence: 99%

Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions

et al. 2015

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Opioid-related deaths, abuse, and drug interactions are growing epidemic problems that have medical, social, and economic implications. Drug transporters play a major role in the disposition of many drugs, including opioids; hence they can modulate their pharmacokinetics, pharmacodynamics and their associated drug-drug interactions (DDIs). Our understanding of the interaction of transporters with many therapeutic agents is improving; however, investigating such interactions with opioids is progressing relatively slowly despite the alarming number of opioids-mediated DDIs that may be related to transporters. This review presents a comprehensive report of the current literature relating to opioids and their drug transporter interactions. Additionally, it highlights the emergence of transporters that are yet to be fully identified but may play prominent roles in the disposition of opioids, the growing interest in transporter genomics for opioids, and the potential implications of opioid-drug transporter interactions for cancer treatments. A better understanding of drug transporters interactions with opioids will provide greater insight into potential clinical DDIs and could help improve opioids safety and efficacy.

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Moving toward Personalized Medicine in the Methadone Maintenance Treatment Program: A Pilot Study on the Evaluation of Treatment Responses in Taiwan

Cited by 18 publications

References 51 publications

Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African–Americans with opioid use disorder

Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African–Americans with opioid use disorder

Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study

Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions

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