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Open research questions in Pharmacogenetics and Drug Metabolism

513 gap statements mined from Pharmacogenetics and Drug Metabolism papers in our 7.9M-paper local library, which holds 2,261 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Finally, pharmacist-led pharmacokinetic optimization is itself under-studied as an intervention; prospective evaluation of its effect on exposure, toxicity, adherence, and outcome would strengthen the evidentiary basis for the practice model proposed here. Real-world pharmacokinetic data remain limited, so the exposure variability actually experienced in practice is incompletely characterized.

    Food Effects, Pharmacokinetic Drug–Drug Interactions, and Clinical Optimization of Oral Anticancer Agents · 2026 · DOI

  • An important limitation of the oral dose simulations is that the available clinical datasets in patients with hepatic impairment were exclusively intravenous.

    Physiologically based pharmacokinetic modeling of diazepam: quantitative assessment of hepatic impairment and model-informed dose optimization in patients with liver cirrhosis · 2026 · DOI

  • A further limitation is that this review did not differentiate pharmacokinetic from pharmacodynamic interactions, although this distinction has important clinical implications and should be explored in future studies. First, it was not possible to describe DDIs for every agent considered, as evidence in the literature is scarce.

    Pharmacological interactions between psychotropic drugs and anticancer treatments: implications for clinical practice · 2026 · DOI

  • Further work that considers how the value of personalized medicine varies with different stakeholders, including healthcare professionals, patients, and hospital facilities, is needed.

    New Personalized Medicine Model for Medication Management · 2026 · DOI

  • Future efforts should focus on developing interoperable, scalable pharmacogenomic CDS systems that can be seamlessly integrated across diverse healthcare settings, including primary care and community pharmacies.

    Bridging the Gap Between Pharmacogenomic Discovery and Clinical Implementation: Insights from Selected Studies on Inter-Individual Variability in Drug Response · 2026 · DOI

  • They do not establish a treatment effect or drug– drug interaction because sampling was sparse, one codeine value was below the verified LOQ, CT7 was influential despite duplicate confirmation, plasma-testosterone availability was unequal, and formulation and control-matching limitations remained.

    Codeine and Testosterone Concentration Patterns During Co-Administration of Codeine and Testosterone Undecanoate in Male Wistar Rats · 2026 · DOI

  • The direct interaction interface between CYP3A4 and UGT1A7 has not yet been identified, and the conformational changes induced by residue 208 substitutions remain unknown.

    Residue 208 of UGT1A7 Determines the Functional Consequences of CYP3A4-UGT1A7 Association in Living Cells · 2026 · DOI

  • Further studies using independent samples are therefore required to validate the results and confirm breed-specificity.

    Development and qualification of recombinant Göttingen Minipig CYP3A22 and CYP3A29 · 2026 · DOI

  • Lack of recombinant CYP3A enzymes for Göttingen Minipigs. Need for characterization of the catalytic properties of these enzymes. Gap in the use of Göttingen Minipigs as a nonclinical species in drug development.

    Development and qualification of recombinant Göttingen Minipig CYP3A22 and CYP3A29 · 2026 · DOI

  • Beyond these enzymes, other cytochrome P450 variants and pharmacologically relevant genes may also exhibit population-specific patterns that warrant further investigation.

    Major Allele Frequencies in CYP2C9 and CYP2C19 in Asian and European Populations: A Case Study to Disaggregate Data Among Large Racial Categories · 2025 · DOI

  • Current prescribing guidelines may be limited by evidence derived from clinical trials with insufficient representation of ethnic minority populations, potentially compromising their generalizability. Future clinical trials should prioritize inclusive recruitment strategies that span multiple geographic regions and demographic groups to enhance external validity and ensure equitable evidence generation.

    Major Allele Frequencies in CYP2C9 and CYP2C19 in Asian and European Populations: A Case Study to Disaggregate Data Among Large Racial Categories · 2025 · DOI

  • Future studies should investigate the clinical relevance of the findings from this study by incorporating larger sample size, human subjects, protein expression and activity data, as well as pharmacokinetic and pharmacodynamic parameters. 50—55 Therefore, this sex-dependent regulation of NAT2 by the D614G variant warrants further investigation into potential disease-sex-genedrug interactions.

    RETRACTED: Severe acute respiratory syndrome coronavirus 2–mediated dysregulation of drug processing genes is dependent on pathogenic variants, target site of infection, age, and sex · 2025 · DOI

  • Genetic polymorphisms such as the CYP2C41 gene deletion can alter CYP activity and influence drug interactions, although not well characterized in dogs.

    Adverse Drug–Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs · 2025 · DOI

  • There is a need to assess CYP2D6 polymorphism in clinical pediatric psychiatric practice.

    The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis—A Prospective Study · 2024 · DOI

  • However, less attention has been credited to the effects on non-CYP phase I and phase II drug metabolism, and especially data on the effects of inflammation on DME activity is lacking.

    CYP P450 and non-CYP P450 Drug Metabolizing Enzyme Families Exhibit Differential Sensitivities towards Proinflammatory Cytokine Modulation · 2024 · DOI

  • Although it lacks about one-third of the coding sequence, it remains unknown whether, or to which degree, the truncation impacts function.

    Clinical Function Assignment of NAT2 Alleles by the Clinical Pharmacogenetics Implementation Consortium Pharmacogene Curation Expert Panel · 2026 · DOI

  • Future research should investigate whether genotype-based dosing improves long-term outcomes, such as recovery time, postoperative nausea and vomiting, or cognitive function.

    CYP2C9-dependent variability in propofol pharmacokinetics and hemodynamic effects: A population-based pharmacogenetic study · 2026 · DOI

  • These observations remain hypothesis-generating and warrant further investigation in studies with appropriate comparison groups, standardized clinical assessment, and pharmacokinetic measurements.

    Liver enzyme elevations during statin–ezetimibe therapy in ABCG2 c.421C>A variant carriers: a case series and narrative review · 2026 · DOI

  • Additional biomarkers have been explored, although current evidence is insufficient to support clinical implementation; nevertheless, the emerging biomarkers remain promising candidates for future investigation.

    Implementation of a Pharmacogenetic Strategy for Statin Therapy in the Spanish National Health System: A Systematic Review and Regulatory Framework Analysis · 2026 · DOI

  • PBPK modeling is already recognized as a new alternative method that is gaining traction and credibility depending upon its application. Several groups are adding layers to the usefulness and testing the intersection of artificial intelligence and PBPK modeling.

    Applications of PBPK Modeling to Estimate Drug Metabolism and Related ADME Processes in Specific Populations · 2025 · DOI

  • So far, many strategies have been developed to optimize the electron transfer process in P450s catalytic systems to improve the catalytic efficiency of P450s, and calculations such as molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) are used to elucidate the electron transfer mechanism of P450s.

    Engineering Electron Transfer Pathway of Cytochrome P450s · 2024 · DOI

  • However, the detailed mechanisms through which PXR signaling regulates lipid homeostasis are not completely understood.

    Sulforaphane Attenuates Antipsychotic-Elicited Hypercholesterolemia Through Inhibition of Pregnane X Receptor · 2026 · DOI

  • In this Perspective, we have reviewed recent advances in experimental and computational approaches used to investigate the mechanisms underlying the CPR-mediated…

    Recent Advances in Elucidating the Mechanism of the NADPH–Cytochrome P450 Reductase-Mediated Electron Transfer Cycle: Experimental and Computational Perspectives · 2025 · DOI

  • Leveraging Large Language Models (LLMs) Clinical Decision Support (CDS) Phenoconversion calculators and combined genotype prediction models Increased genomic diversity and PGx integration into drug development pipelines Prioritization of High Yield Fields and Groups 3.1.

    Clinician Experiences at the Frontier of Pharmacogenomics and Future Directions · 2025 · DOI

  • Small sample size of 56 patients, - Limited to a pediatric Romanian population, - No mention of long-term follow-up beyond 12…

    The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis—A Prospective Study · 2024 · DOI

Most-cited papers in Pharmacogenetics and Drug Metabolism

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Open questions raised by papers listed on this page include: (1) Real-world pharmacokinetic data remain limited, so the exposure variability actually experienced in practice is incompletely characterized (“Food Effects, Pharmacokinetic Drug–Drug Interactions, and Clinical Optimization…”, 2026); (2) It was not possible to describe DDIs for every agent considered, as evidence in the literature is scarce (“Pharmacological interactions between psychotropic drugs and anticancer…”, 2026); (3) Further work that considers how the value of personalized medicine varies with different stakeholders, including healthcare professionals, patients, and hospital facilities, is needed (“New Personalized Medicine Model for Medication Management”, 2026); (4) The direct interaction interface between CYP3A4 and UGT1A7 has not yet been identified, and the conformational changes induced by residue 208 substitutions remain unknown (“Residue 208 of UGT1A7 Determines the Functional Consequences of CYP3A4-UGT1A7…”, 2026); (5) Although it lacks about one-third of the coding sequence, it remains unknown whether, or to which degree, the truncation impacts function (“Clinical Function Assignment of NAT2 Alleles by the Clinical Pharmacogenetics…”, 2026). 513 gap statements have been mined from Pharmacogenetics and Drug Metabolism papers in our 7.9M-paper local library, which holds 2,261 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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