The Value of CYP2D6 and OPRM1 Pharmacogenetic Testing for Opioid Therapy

Reynolds, Kristen K.; Ramey-Hartung, Bronwyn; Jortani, Saeed A.

doi:10.1016/j.cll.2008.10.003

Cited by 20 publications

(8 citation statements)

References 41 publications

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“…Other possible explanations could be a pharmacodynamic influence in the reluctance of a considerable group of patients to increase methadone dose. The candidate gene OPRM1 has previously been related to opioid treatment response, mainly in analgesia and alcohol dependence [47], [64], [65]. The more commonly studied SNP (A118G), in the mu-opioid receptor gene can affect opioid function.…”

Section: Discussionmentioning

confidence: 99%

Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response

et al. 2011

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Although the efficacy of methadone maintenance treatment (MMT) in opioid dependence disorder has been well established, the influence of methadone pharmacokinetics in dose requirement and clinical outcome remains controversial. The aim of this study is to analyze methadone dosage in responder and nonresponder patients considering pharmacogenetic and pharmacokinetic factors that may contribute to dosage adequacy. Opioid dependence patients (meeting Diagnostic and Statistical Manual of Mental Disorders, [4th Edition] criteria) from a MMT community program were recruited. Patients were clinically assessed and blood samples were obtained to determine plasma concentrations of (R,S)-, (R) and (S)- methadone and to study allelic variants of genes encoding CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, and P-glycoprotein. Responders and nonresponders were defined by illicit opioid consumption detected in random urinalysis. The final sample consisted in 105 opioid dependent patients of Caucasian origin. Responder patients received higher doses of methadone and have been included into treatment for a longer period. No differences were found in terms of genotype frequencies between groups. Only CYP2D6 metabolizing phenotype differences were found in outcome status, methadone dose requirements, and plasma concentrations, being higher in the ultrarapid metabolizers. No other differences were found between phenotype and responder status, methadone dose requirements, neither in methadone plasma concentrations. Pharmacokinetic factors could explain some but not all differences in MMT outcome and methadone dose requirements.

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Section: Discussionmentioning

confidence: 99%

Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response

et al. 2011

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“…As noted by Reynolds et al [12], with the knowledge of a patient’s potential for positive response to a given pain medicine, a physician is armed with critical information that can guide therapeutic decisions in real time. The incorporation of pharmacogenetic biomarkers holds promise as a means of assessing a patient’s risk of adverse events or likelihood of drug efficacy.…”

Section: Resultsmentioning

confidence: 99%

“…This enzyme system is extensively involved in the metabolism of drugs as well as other chemicals, foods, or toxins in the body. Although more than 30 CYP450 isoenzymes have been identified, seven of these are clinically important: CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4, whose presence and activity levels vary based on a variety of factors including race, ethnic background and tobacco abuse [9] as well as interactions with other medication, and other receptors, such as the opioid receptors [12]. …”

Section: Opioid Metabolismmentioning

confidence: 99%

“…Whether the patient possesses the wild-type (two normal copies), heterozygous (one normal, one altered) or homozygous (two altered copies) alleles of this gene has been shown to influence postoperative opioid requirement after abdominal surgery [9]. One of the best-studied OPRM1 SNPs is 118A/G, with the G variant seen in 10–48% of tested patients, depending on the study [12]. Reynolds et al found that patients carrying the GG genotype required much higher opioid doses to achieve pain relief [12].…”

Section: Opioid Metabolismmentioning

confidence: 99%

“…One of the best-studied OPRM1 SNPs is 118A/G, with the G variant seen in 10–48% of tested patients, depending on the study [12]. Reynolds et al found that patients carrying the GG genotype required much higher opioid doses to achieve pain relief [12]. …”

Section: Opioid Metabolismmentioning

confidence: 99%

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Genetic Testing for Opioid Pain Management: A Primer

2017

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Patients see their primary care physicians (PCPs) for a variety of medical conditions, chronic pain being one of the most common. An increased use of prescription medications (especially opioids) has led to an increase in adverse drug reactions and has heightened our awareness of the variability in response to medications. Opioids and other pain adjuvants are widely used, and drug–drug interactions involving these analgesics can be problematic and potentially lethal. Pharmacogenetics has improved our understanding of drug efficacy and response, opened doors to individual tailoring of medical management, and created a series of ethical and economic considerations. Since it is a relatively new field, genetic testing has not been fully integrated into the primary care setting. The purpose of this paper is to review the metabolism of commonly prescribed opioids, discuss the economic and ethical issues, and provide PCPs with an understanding of how to incorporate genetic testing into routine use to improve clinical practice and patient management.

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