Browsing by Author "Somogyi, Andrew A."

Now showing 1 - 4 of 4
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    Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update
    (Wiley, 2021) Karnes, Jason H.; Rettie, Allan E.; Somogyi, Andrew A.; Huddart, Rachel; Fohner, Alison E.; Formea, Christine M.; Lee, Ming Ta Michael; Llerena, Adrian; Whirl-Carrillo, Michelle; Klein, Teri E.; Phillips, Elizabeth J.; Mintzer, Scott; Gaedigk, Andrea; Caudle, Kelly E.; Callaghan, John T.; Medicine, School of Medicine
    Phenytoin is an antiepileptic drug with a narrow therapeutic index and large interpatient pharmacokinetic variability, partly due to genetic variation in CYP2C9. Furthermore, the variant allele HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for the use of phenytoin based on CYP2C9 and/or HLA-B genotypes (updates on cpicpgx.org).
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    Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2B6 Genotype and Methadone Therapy
    (Wiley, 2024) Robinson, Katherine M.; Eum, Seenae; Desta, Zeruesenay; Tyndale, Rachel F.; Gaedigk, Andrea; Crist, Richard C.; Haidar, Cyrine E.; Myers, Alan L.; Samer, Caroline F.; Somogyi, Andrew A.; Zubiaur, Pablo; Iwuchukwu, Otito F.; Whirl-Carrillo, Michelle; Klein, Teri E.; Caudle, Kelly E.; Donnelly, Roseann S.; Kharasch, Evan D.; Medicine, School of Medicine
    Methadone is a mu (μ) opioid receptor agonist used clinically in adults and children to manage opioid use disorder, neonatal abstinence syndrome, and acute and chronic pain. It is typically marketed as a racemic mixture of R- and S-enantiomers. R-methadone has 30-to 50-fold higher analgesic potency than S-methadone, and S-methadone has a greater adverse effect (prolongation) on the cardiac QTc interval. Methadone undergoes stereoselective metabolism. CYP2B6 is the primary enzyme responsible for catalyzing the metabolism of both enantiomers to the inactive metabolites, S- and R-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (S- and R-EDDP). Genetic variation in the CYP2B6 gene has been investigated in the context of implications for methadone pharmacokinetics, dose, and clinical outcomes. Most CYP2B6 variants result in diminished or loss of CYP2B6 enzyme activity, which can lead to higher plasma methadone concentrations (affecting S- more than R-methadone). However, the data do not consistently indicate that CYP2B6-based metabolic variability has a clinically significant effect on methadone dose, efficacy, or QTc prolongation. Expert analysis of the published literature does not support a change from standard methadone prescribing based on CYP2B6 genotype (updates at www.cpicpgx.org).
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    Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy
    (Wiley, 2021) Crews, Kristine R.; Monte, Andrew A.; Huddart, Rachel; Caudle, Kelly E.; Kharasch, Evan D.; Gaedigk, Andrea; Dunnenberger, Henry M.; Leeder, J. Steven; Callaghan, John T.; Samer, Caroline Flora; Klein, Teri E.; Haidar, Cyrine E.; Van Driest, Sara L.; Ruano, Gualberto; Sangkuhl, Katrin; Cavallari, Larisa H.; Müller, Daniel J.; Prows, Cynthia A.; Nagy, Mohamed; Somogyi, Andrew A.; Skaar, Todd C.; Medicine, School of Medicine
    Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes which have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol-O-methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1 and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone and methadone and for OPRM1 and COMT for clinical use.
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    PharmVar GeneFocus: CYP2B6
    (Wiley, 2021) Desta, Zeruesenay; El-Boraie, Ahmed; Gong, Li; Somogyi, Andrew A.; Lauschke, Volker M.; Dandara, Collet; Klein, Kathrin; Miller, Neil; Klein, Teri E.; Tyndale, Rachel F.; Whirl-Carrillo, Michelle; Gaedigk, Andrea; Medicine, School of Medicine
    The Pharmacogene Variation Consortium (PharmVar) catalogs star (*) allele nomenclature for the polymorphic human CYP2B6 gene. Genetic variation within the CYP2B6 gene locus impacts the metabolism or bioactivation of clinically important drugs. Of particular importance are efficacy and safety concerns regarding: efavirenz, which is used for the treatment of HIV type-1 infection; methadone, a mainstay in the treatment of opioid use disorder and as an analgesic; ketamine, used as an antidepressant and analgesic; and bupropion, which is prescribed to treat depression and for smoking cessation. This GeneFocus provides a comprehensive overview and summary of CYP2B6 and describes how haplotype information catalogued by PharmVar is utilized by the Pharmacogenomics Knowledgebase (PharmGKB) and the Clinical Pharmacogenetics Implementation Consortium (CPIC).