Review
Pharmacology & Pharmacy
Michael Pacanowski, Julia Vitarello, Insoo Hyun, Timothy Yu, Issam Zineh
Summary: Precision medicine has evolved from the application of pharmacogenetic biomarkers for targeted therapies to the development of individualized medicines for very small numbers of patients, offering unprecedented opportunities for patients with severe diseases. However, it also presents complex challenges in terms of scientific advancement, clinical practice, and regulatory aspects.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Cardiac & Cardiovascular Systems
Emma Forton Magavern, Juan Carlos Kaski, Richard M. Turner, Heinz Drexel, Azara Janmohamed, Andrew Scourfield, Daniel Burrage, Christopher N. Floyd, Elizabeth Adeyeye, Juan Tamargo, Basil S. Lewis, Keld Per Kjeldsen, Alexander Niessner, Sven Wassmann, Patrick Sulzgruber, Pascal Borry, Stefan Agewall, Anne Grete Semb, Gianluigi Savarese, Munir Pirmohamed, Mark J. Caulfield
Summary: There is a growing body of evidence supporting the use of pharmacogenomics in cardiovascular pharmacology, but international cardiovascular societies lack a common position on the diverse availability, interpretation, and application of such data, as well as the challenges presented by variations in clinical practice across European countries. In addition to barriers to implementing pharmacogenomic testing and complexity in acting on results, there are disparities in the availability of resources and expertise internationally within Europe. Legal and ethical considerations for genomic testing and clinical therapeutic application also require serious thought.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
(2022)
Article
Cardiac & Cardiovascular Systems
Emma F. Magavern, Juan Carlos Kaski, Richard M. Turner, Heinz Drexel, Azara Janmohamed, Andrew Scourfield, Daniel Burrage, Christopher N. Floyd, Elizabeth Adeyeye, Juan Tamargo, Basil S. Lewis, Keld Per Kjeldsen, Alexander Niessner, Sven Wassmann, Patrick Sulzgruber, Pascal Borry, Stefan Agewall, Anne Grete Semb, Gianluigi Savarese, Munir Pirmohamed, Mark J. Caulfield
Summary: Pharmacogenomics shows promise in advancing cardiovascular therapy, but faces practical barriers in implementation within Europe due to differences in populations, resources, expertise, and ethical-legal frameworks. Clinical workforce upskilling is crucial, along with the development of digital infrastructure and clinical support tools to bridge healthcare delivery gaps and promote health equality.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
(2022)
Editorial Material
Rheumatology
Mohamed Hassan Abu-Zaid, Adewale Adebajo, Yasser El Miedany
Summary: Biosimilars are similar products to reference biologic products, but their regulatory approval in Africa is still under development. Currently, there are limited biosimilars available for treating rheumatic diseases in Africa. The use of biosimilars in Africa provides an important opportunity to expand access to biologic drugs for rheumatology patients. This editorial highlights the potential benefits, challenges, and current efforts surrounding the use of biosimilars in Africa's rheumatology field.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Review
Pharmacology & Pharmacy
Emma F. Magavern, Deepti Gurdasani, Fu L. Ng, Sandra Soo-Jin Lee
Summary: Pharmacogenomics is increasingly being integrated into clinical practice, but the inclusion of diverse populations is essential to avoid widening health disparities. This review highlights the importance of addressing potential pitfalls and gaps in evidence to promote health equality and raise awareness among prescribers.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Emilio Berna-Rico, Javier Perez-Bootello, Carlota Abbad-Jaime de Arago, Alvaro Gonzalez-Cantero
Summary: Psoriasis is a chronic inflammatory disease with a genetic background. Genetic variations in HLA-Cw*06 allele and genes related to inflammation and keratinocyte proliferation have been associated with disease development. This review assessed the evidence on how these genetic variations may affect the response to psoriasis treatment. Variations in VDR gene may influence topical vitamin D and phototherapy response, while variations in ABC transporter genes are associated with methotrexate and cyclosporine outcomes. Multiple single-nucleotide polymorphisms related to anti-TNF-α response modulation show conflicting results. HLA-Cw*06 has been extensively studied and related to ustekinumab response. Further research is needed to establish the usefulness of these genetic biomarkers in clinical practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Tilman D. Rachner, Robert Coleman, Peyman Hadji, Lorenz C. Hofbauer
Summary: Antiresorptive therapy plays a crucial role in the multimodal treatment of patients with advanced malignancies and metastatic bone disease, improving overall survival and long-term disease control. Emerging clinical studies demonstrate the benefits of initial antiresorptive therapy using bisphosphonates or denosumab, but adverse events like osteonecrosis of the jaw may occur with cumulative doses. There is a growing clinical need for new antiresorptive concepts to treat long-term survivors.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Review
Cardiac & Cardiovascular Systems
E. F. Magavern, J. C. Kaski, R. M. Turner, A. Janmohamed, P. Borry, M. Pirmohamed
Summary: Pharmacogenomics plays a burgeoning role in cardiovascular medicine, with recent developments in sequencing bringing personalized medicine closer to reality. Further research, guidance, and technological adaptation are needed to fully realize the potential of pharmacogenomics in improving patient care.
CARDIOVASCULAR DRUGS AND THERAPY
(2021)
Review
Neurosciences
Jia-Si Liu, Ying Chen, Dan-Dan Shi, Bao-Rong Zhang, Jia-Li Pu
Summary: Parkinson's disease (PD) is a common neurodegenerative disease with significant inter-individual variability in treatment effectiveness. This review explores the impact of gene polymorphism on the efficacy of anti-parkinsonian drugs and highlights the need for further research in this area.
CURRENT NEUROPHARMACOLOGY
(2023)
Review
Pediatrics
Aaqib Zaffar Banday, Rahila Nisar, Pratap Kumar Patra, Imtiyaz Ahmad, Anju Gupta
Summary: The spectrum of pediatric rheumatological disorders is diverse and important in differential diagnosis. Basic investigations such as complete blood count, biochemical assays, urine analysis, and autoantibodies tests provide evidence for diagnosis, exclude other diseases, and monitor disease activity. Imaging and tissue biopsies are used to confirm the diagnosis depending on the clinical features.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Pediatrics
Edward L. Schor, David Bergman
Summary: Well-child care is a universal service for young children that requires personalized care based on individual and family needs. Reconsidering the traditional schedule of preventive care visits and providing comprehensive care over a series of visits will lead to more efficient and effective preventive care. This model of care will require changes in training, responsibilities, and reimbursement of healthcare team members, as well as enhanced communication and collaboration among all parties involved, particularly with families.
Review
Pharmacology & Pharmacy
Xuerong Yang, Qi Li, Yuanyuan He, Yulian Zhu, Rou Yang, Xiaoshi Zhu, Xi Zheng, Wei Xiong, Yong Yang
Summary: IgAV nephritis is a chronic kidney disease caused by inflammation and IgA deposition in small blood vessels in the kidneys. Current treatment principles include drug therapy, support measures, and prevention of complications. Genetic information can help predict drug response and provide safer and more effective treatment for children.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pediatrics
Kristie N. Ramos, David Gregornik, Kenneth S. Ramos
Summary: This review discusses the potential of pharmacogenomics in optimizing medication dosing regimens and preventing medication toxicity, focusing on thiopurines, anthracyclines, and vincristine. It also highlights recent findings on pharmacogenomic guidance and important areas for future investments in the study of precision survivorship.
CURRENT OPINION IN PEDIATRICS
(2021)
Review
Pediatrics
Masa Bizjak, Merav Heshin-Bekenstein, Marc H. A. Jansen, Amit Ziv, Saskya Angevare, Yosef Uziel, Nicolaas M. M. Wulffraat, Natasa Toplak
Summary: With the introduction of biological disease-modifying antirheumatic drugs (bDMARDs), the treatment of pediatric patients with autoimmune/inflammatory rheumatic diseases (pedAIIRD) has significantly improved. However, the use of these drugs has increased the risk of infections, making infection prevention a top priority. Vaccination is the most effective preventive measure against infections.
FRONTIERS IN PEDIATRICS
(2023)
Review
Chemistry, Medicinal
Tracy Sandritter, Rachel Chevalier, Rebecca Abt, Valentina Shakhnovich
Summary: Gastroenterologists have been early adopters of precision medicine through pharmacogenetic testing, specifically genotyping for TPMT before prescribing 6-mercaptopurine or azathioprine. While pharmacogenetic testing for drug dose individualization has become more available, interpreting results for drugs other than 6-mercaptopurine and azathioprine remains challenging, limiting widespread implementation of genotype-guided dosing.
Article
Pharmacology & Pharmacy
Kristine R. Crews, Andrew A. Monte, Rachel Huddart, Kelly E. Caudle, Evan D. Kharasch, Andrea Gaedigk, Henry M. Dunnenberger, J. Steven Leeder, John T. Callaghan, Caroline Flora Samer, Teri E. Klein, Cyrine E. Haidar, Sara L. Van Driest, Gualberto Ruano, Katrin Sangkuhl, Larisa H. Cavallari, Daniel J. Muller, Cynthia A. Prows, Mohamed Nagy, Andrew A. Somogyi, Todd C. Skaar
Summary: Opioids are commonly used for the treatment of acute and chronic pain, and the clinical effects and adverse events are associated with genes such as CYP2D6, OPRM1, and COMT. While there is extensive research on the association between CYP2D6 and codeine/tramadol, data for hydrocodone, oxycodone, methadone, OPRM1, and COMT are more limited.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Pharmacology & Pharmacy
Brian D. Chapron, Alenka Chapron, J. Steven Leeder
Summary: Developmental changes in childhood impact drug disposition, with advancements in understanding over the past 20 years driven by technological progress in mass spectrometry and in silico tools. However, gaps in research evidence highlight areas where further characterization of developmental trends in drug disposition is needed.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Chelsea Hosey-Cojocari, Sherwin S. Chan, Chance S. Friesen, Amie Robinson, Veronica Williams, Erica Swanson, Daniel O'Toole, Jansynn Radford, Neil Mardis, Trevor N. Johnson, J. Steven Leeder, Valentina Shakhnovich
Summary: The liver is the primary organ responsible for clearing most drugs, the clearance capacity is related to organ size and growth in children. Equations relating body surface area and liver volume can adequately estimate liver volumes in children, regardless of weight status.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2021)
Article
Pharmacology & Pharmacy
Yaowaluck Hongkaew, Wendy Y. Wang, Roger Gaedigk, Chonlaphat Sukasem, Andrea Gaedigk
Summary: This study aimed to investigate inconsistent or suspicious CYP2D6 Luminex xTAG genotype calls among Thai subjects, identifying a high number of false genotype calls and revealing three novel haplotypes, two of which are nonfunctional. The findings highlight the importance of systematic characterization of the CYP2D6 locus in diverse populations and rigorous platform validation.
Review
Pharmacology & Pharmacy
Daniel L. Hertz, Laura B. Ramsey, Mathangi Gopalakrishnan, J. Steven Leeder, Sara L. Van Driest
Summary: Pharmacogenetics aims to select the right drug and dose for each patient to optimize therapeutic outcomes, with a focus on pharmacokinetics. Efforts to discover and validate pharmacogenetics-pharmacodynamics associations without the confounding of pharmacokinetic variability could provide valuable insights for future analyses.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Stephani L. Stancil, Whitney Nolte, Robin E. Pearce, Vincent S. Staggs, J. Steven Leeder
Summary: This study aimed to investigate the factors influencing the biotransformation of naltrexone. The results showed that there is significant variability in naltrexone biotransformation in both children and adults, and it is influenced by age, sex, and genetic variation.
DRUG METABOLISM AND DISPOSITION
(2022)
Article
Pharmacology & Pharmacy
Deepak Ahire, Abdul Basit, Lisa J. Christopher, Ramaswamy Iyer, J. Steven Leeder, Bhagwat Prasad
Summary: The mitochondrial amidoxime-reducing component (mARC) enzymes, which metabolize various substances, were quantified in different tissues using targeted proteomics. The abundance of mARC1 and mARC2 in the liver, kidney, intestine, and lung was determined, and their levels were found to be independent of age and sex. These findings provide important information for developing pharmacokinetic models and predicting the metabolism of mARC substrates in vivo.
DRUG METABOLISM AND DISPOSITION
(2022)
Article
Pharmacology & Pharmacy
Xiaoyan Chu, Bhagwat Prasad, Sibylle Neuhoff, Kenta Yoshida, James Steven Leeder, Dwaipayan Mukherjee, Kunal Taskar, Manthena V. S. Varma, Xinyuan Zhang, Xinning Yang, Aleksandra Galetin
Summary: The role of membrane transporters in pharmacokinetics, drug-drug interactions, pharmacodynamics, and drug toxicity is widely recognized. This article highlights recent advances in the study of changes in transporter expression and activity in various diseases and specific populations, with a focus on clinical implications.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Andrew C. Behrle, Justin Douglas, J. Steven Leeder, Leon van Haandel
Summary: CYP2D6 is an important enzyme involved in the metabolism of clinically used drugs. This study aimed to identify an endogenous urinary biomarker of CYP2D6 activity. The researchers isolated and purified a substance called M1 from urine, and found that it has a similar structure to solanidine, a nitrogen-containing steroidal alkaloid. This discovery may have implications for assessing CYP2D6 activity and guiding treatment with drugs metabolized by this enzyme.
DRUG METABOLISM AND DISPOSITION
(2022)
Article
Medicine, Research & Experimental
J. Steven Leeder, Andrea Gaedigk, Krista J. Wright, Vincent S. Staggs, Sarah E. Soden, Yvonne S. Lin, Robin E. Pearce
Summary: This study aimed to investigate the relative contributions of genetic variation, growth, and development on CYP2D6 activity during puberty. Through a three-year longitudinal study on healthy children and adolescents aged 7-15 years, it was found that CYP2D6 genotype was the most important factor contributing to the variability in CYP2D6 activity during puberty, while age and pubertal development had minimal effects. The use of genotype-based dosing guidelines should be considered for CYP2D6 substrates in pediatric patients.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Pablo Zubiaur, Paula Soria-Chacartegui, Erin C. C. Boone, Bhagwat Prasad, Jean Dinh, Wendy Y. Y. Wang, Santiago Zugbi, Andrea Rodriguez-Lopez, Eva Gonzalez-Iglesias, J. Steven Leeder, Francisco Abad-Santos, Andrea Gaedigk
Summary: A novel haplotype, CYP2C:TG, composed of two non-coding variants, was found to be associated with ultrarapid metabolism of CYP2C19 substrates. However, further analysis revealed that the CYP2C:TG haplotype had no significant effect on the pharmacokinetics of these substrates or the protein abundance and activity of CYP2C8, CYP2C9, CYP2C18, and CYP2C19. On the other hand, CYP2C19 intermediate and poor metabolizers showed distinct differences compared to normal, rapid, and ultrarapid metabolizers. In conclusion, there is insufficient evidence to support the clinical testing of the CYP2C:TG haplotype for drug therapy.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Clinical Neurology
Rose Gelineau-Morel, Christopher Smyser, J. Steven Leeder
Summary: The recent focus on improving recognition of dystonia in cerebral palsy (DCP) has highlighted the need for more effective treatments. Current pharmacologic recommendations for DCP are based on anecdotal evidence, with minimal to moderate improvements in dystonia. Precision therapeutics can improve treatment outcomes through predictive biomarker identification, patient stratification, individualized interventions, and monitoring of response.
Meeting Abstract
Pharmacology & Pharmacy
K. Feldman, R. Pearce, G. Kearns, J. Leeder, S. Abdel-Rahman, V. Staggs, A. Friesen, A. Gaedigk, J. Weigel, V. Shakhnovich
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Meeting Abstract
Pharmacology & Pharmacy
C. Hosey-Cojocari, S. Chan, C. Friesan, E. Swanson, D. O'Toole, N. Mardis, J. Leeder, V. Shakhnovich
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Meeting Abstract
Pharmacology & Pharmacy
V. Shakhnovich, S. Abdel-Rahman, S. Chan, N. Mardis, R. Pearce, V. Williams, C. Friesen, J. Radford, J. Leeder
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)