Review
Genetics & Heredity
H. J. Weng, T. F. Tsai
Summary: ABCB1 is a crucial protein in skin that is involved in drug transport and treatment responsiveness. It is also associated with the pathogenesis of several dermatoses, warranting further investigation into its roles in dermatology.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Genetics & Heredity
Agnieszka Jelen, Rafal Swiechowski, Marta Zebrowska-Nawrocka, Aleksandra Salagacka-Kubiak, Dagmara Szmajda-Krygier, Piotr Ga Lecki, Ewa Balcerczak
Summary: This study evaluated the association between ABCB1 gene polymorphism and depression, as well as the effectiveness of its treatment. The results showed that T-129C does not play an important role in rDD development, but other studied SNPs do have an additive impact on the course of depression and its treatment effectiveness.
Article
Pharmacology & Pharmacy
Nancy H. C. Loos, Irene A. Retmana, Wenlong Li, Margarida L. F. Martins, Maria C. Lebre, Rolf W. Sparidans, Jos H. Beijnen, Alfred H. Schinkel
Summary: In this study using genetically modified mouse models, the influence of various transporters and drug metabolizing enzymes on the pharmacokinetics and tissue distribution of Sotorasib was studied. Results showed that ABCB1 transporter restricted the brain accumulation of Sotorasib, while CYP3A enzyme and OATP1a/1b transporter potentially limited its oral availability. These findings are important for optimizing the clinical use of Sotorasib.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Chemistry, Medicinal
Yaogeng Wang, Rolf W. Sparidans, Sander Potters, Rahime Senturk, Maria C. Lebre, Jos H. Beijnen, Alfred H. Schinkel
Summary: The study showed that ABCG2, especially ABCB1, limit the brain and testis penetration of selpercatinib, while CYP3A-mediated metabolism may affect selpercatinib's oral exposure and tissue concentrations.
Article
Pharmacology & Pharmacy
Yaogeng Wang, Rolf W. Sparidans, Sander Potters, Maria C. Lebre, Jos H. Beijnen, Alfred H. Schinkel
Summary: The study found that ABCG2 and especially ABCB1 significantly limit the brain and testis penetration of pralsetinib, while SLCO1A/1B and CYP3A4 are unlikely to affect its pharmacokinetics. The effects of ABCB1 and ABCG2 can be mostly reversed by the coadministration of the inhibitor elacridar, which may be useful for the further clinical development of pralsetinib.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Medicine, Research & Experimental
Pablo Zubiaur, Paula Soria-Chacartegui, Dora Koller, Marcos Navares-Gomez, Dolores Ochoa, Susana Almenara, Miriam Saiz-Rodriguez, Gina Mejia-Abril, Gonzalo Villapalos-Garcia, Manuel Roman, Samuel Martin-Vilchez, Francisco Abad-Santos
Summary: This study investigated the impact of genetic polymorphisms on olanzapine pharmacokinetics and safety in healthy volunteers. Polymorphisms in genes like CYP2C9, SLC22A1, ABCB1, ABCC2, and APOC3 were found to be associated with olanzapine pharmacokinetic variability. Adverse reactions were also related to genes such as ABCB1, SL22A1, DRD2, and CYP2C9. Further research in patients is needed to validate these findings.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Medicine, Research & Experimental
Leen Magarbeh, Ilona Gorbovskaya, Bernard Le Foll, Reuven Jhirad, Daniel J. Muller
Summary: Pharmacogenetic evidence supports the association between CYP2D6 genetic variants and opioid metabolism, with CPIC guidelines recommending avoidance of tramadol in poor and ultrarapid metabolizers. Although OPRM1 gene suggests increased morphine dosing requirements postoperatively, the clinical relevance remains limited.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Medicinal
Win Lee Edwin Wong, Chiara Fabbri, Benjamin Laplace, Danyang Li, Roos van Westrhenen, Cathryn M. Lewis, Gavin Stewart Dawe, Allan H. Young
Summary: This study suggests that CYP2C19 genotypes, and consequently metabolic phenotypes, may play a role in determining clinical responses to SSRIs, particularly escitalopram and citalopram. However, further investigation is needed to better understand this relationship.
Article
Genetics & Heredity
Grace Zdesenko, Takafira Mduluza, Francisca Mutapi
Summary: This study investigates genetic variations in drug-metabolizing cytochrome P450 enzymes in Zimbabwean patients with schistosomiasis and identifies key genetic variants associated with the efficacy of praziquantel treatment.
FRONTIERS IN GENETICS
(2022)
Article
Pharmacology & Pharmacy
Alexandr Chernov, Daria Kilina, Tatiana Smirnova, Elvira Galimova
Summary: The ABCB1 genetic variants, particularly the C1236T, G2677T/A, and C3435T SNPs, are significantly associated with a negative response to cyclosporine therapy in Russian psoriasis patients. Further studies are needed to validate these findings in different ethnic populations prior to clinical application.
Review
Pharmacology & Pharmacy
Laurence McEvoy, Joanne Cliff, Daniel F. Carr, Andrea Jorgensen, Rosemary Lord, Munir Pirmohamed
Summary: Taxane-induced peripheral neuropathy (TIPN) is a significant issue in cancer therapy, leading to treatment cessation and reduced quality of life. Genetic polymorphisms in the CYP3A family have been studied for their association with TIPN, but the results are inconsistent. This study found that diabetes is significantly associated with the development of TIPN, while CYP3A genotype or phenotype does not appear to play a major role.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Keishi Yamasaki, Muneaki Hidaka, Yohei Kawano, Yumiko Furuya, Hiroshige Ono, Kazuhiko Arimori
Summary: The study found that enhancing intestinal absorption of irinotecan by inhibiting intestinal P-glycoprotein (P-gp) can increase its oral bioavailability, which is one of the main reasons for its limited oral absorption.
JOURNAL OF PHARMACY AND PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Asif Jan, Muhammad Saeed, Ramzi A. Mothana, Tahir Muhammad, Naveed Rahman, Abdullah R. Alanzi, Rani Akbar
Summary: Polymorphism in the CYP2C9 enzyme is known to cause inter-individual differences in drug response. This study investigated the association between the CYP2C9*2 and CYP2C9*3 alleles and the incidence of hypoglycemia in Pakistani patients with type 2 diabetes mellitus. The results suggest that genetic information about a patient's CYP2C9 gene/enzyme can potentially assist physicians in prescribing the most suitable and safest drug based on their genetic makeup.
Article
Neurosciences
Justin Matheson, Yollanda J. Zhang, Bruna Brands, Christine M. Wickens, Arun K. Tiwari, Clement C. Zai, James L. Kennedy, Bernard Le Foll
Summary: Genetic influences on acute responses to psychoactive drugs, specifically the primary psychoactive component of cannabis, may contribute to individual variability in addiction risk. This study found that the ABCB1 gene polymorphism rs2235048 affected the frequency of cannabis use and the metabolism of THC in young adults. Preliminary findings suggest that further research should investigate the role of the ABCB1 gene in cannabis-related phenotypes and the risk of developing a cannabis use disorder.
Article
Medicine, Research & Experimental
Nancy H. C. Loos, Irene A. Retmana, Jamie Rijmers, Yaogeng Wang, Changpei Gan, Maria C. Lebre, Rolf W. Sparidans, Jos H. Beijnen, Alfred H. Schinkel
Summary: Adagrasib (KrazatiTM) is an FDA-approved drug for non-small cell lung cancer (NSCLC) patients with the KRASG12C mutation. The drug's pharmacokinetics were studied in mouse models, revealing the impact of drug transporters and metabolizing enzymes. The study found that ABCB1 and ABCG2 transporters influence the brain penetration of Adagrasib, while CYP3A and Ces1 enzymes strongly impact its oral availability. These findings provide insights into potential drug resistance and drug-drug interactions, which can help optimize the clinical use of Adagrasib.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Medical Laboratory Technology
Florian Lemaitre, Dennis A. Hesselink
THERAPEUTIC DRUG MONITORING
(2023)
Review
Medical Laboratory Technology
Florian Lemaitre, Klemens Budde, Teun Van Gelder, Stein Bergan, Roland Lawson, Ofelia Noceti, Raman Venkataramanan, Laure Elens, Dirk Jan A. R. Moes, Dennis A. Hesselink, Tomasz Pawinski, Kamisha L. Johnson-Davis, Brenda C. M. De Winter, Smita Pattanaik, Merce Brunet, Satohiro Masuda, Loralie J. Langman
Summary: Nirmatrelvir/ritonavir (Paxlovid) is a combination of a peptidomimetic inhibitor (nirmatrelvir) and a pharmacokinetic enhancer (ritonavir) that is approved for the treatment of mild-to-moderate COVID-19. The ritonavir component of this combination can cause significant drug-drug interactions (DDIs) by inhibiting the metabolism of nirmatrelvir. This may lead to higher plasma concentrations of nirmatrelvir and a longer half-life. Co-administration of nirmatrelvir/ritonavir with immunosuppressive drugs (ISDs) is particularly challenging due to the involvement of the same metabolic pathway and the increased risk of adverse drug reactions.
THERAPEUTIC DRUG MONITORING
(2023)
Article
Immunology
Suwasin Udomkarnjananun, Marith Francke, Marjolein Dieterich, Daan van De Velde, Nicolle H. R. Litjens, Karin Boer, Brenda C. M. De Winter, Carla C. Baan, Dennis A. Hesselink
Summary: Transplant recipients may undergo rejection despite maintaining appropriate levels of tacrolimus in the blood. This study examines the concentration of tacrolimus in T-lymphocytes and monocytes, as well as its relationship with FK-binding protein (FKBP)-12 and P-glycoprotein (P-gp) expression. The findings suggest that T-lymphocytes have higher P-gp activity and lower FKBP-12 concentration, which contributes to the lower tacrolimus concentration in these cells.
Article
Nanoscience & Nanotechnology
Liang Wu, Wouter W. Woud, Carla C. Baan, Dennis A. Hesselink, Edwin van der Pol, Guido Jenster, Karin Boer
Summary: This study demonstrates the detection of single urinary extracellular vesicles (uEVs) without isolation using imaging flow cytometry (IFCM). A gate was defined to distinguish uEVs from auto-fluorescent particles, and the final readouts were verified as single EVs. This isolation-free protocol provides a method to quantify and phenotype single uEVs, eliminating the influence of auto-fluorescent particles and protein aggregates.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2023)
Article
Immunology
Hilal Varol, Angela Ernst, Iacopo Cristoferi, Wolfgang Arns, Carla C. Baan, Myrthe van Baardwijk, Thierry van den Bosch, Jennifer Eckhoff, Ana Harth, Dennis A. Hesselink, Folkert J. van Kemenade, Willem de Koning, Christine Kurschat, Robert C. Minnee, Dana A. Mustafa, Marlies E. J. Reinders, Shazia P. Shahzad-Arshad, Malou L. H. Snijders, Dirk Stippel, Andrew P. Stubbs, Jan von der Thusen, Katharina Wirths, Jan U. Becker, Marian C. Clahsen-van Groningen
Summary: This study assessed the feasibility and potential of using NanoString nCounter analysis on KTx biopsies to aid in the classification of rejection in clinical practice. The results showed that transcriptome analysis has the potential to differentiate between different types of kidney transplant rejection and could be valuable in assisting with the classification of kidney transplant rejection.
Article
Radiology, Nuclear Medicine & Medical Imaging
S. Roest, R. P. J. Budde, D. A. Hesselink, F. Zijlstra, M. C. Zillikens, K. Caliskan, D. Bos, O. C. Manintveld
Summary: Osteoporosis is frequently observed in patients after heart transplantation, and further investigation is needed to find appropriate measures to maintain normal bone density in these patients.
CLINICAL RADIOLOGY
(2023)
Article
Peripheral Vascular Disease
Laura E. J. Peeters, Dennis. A. Hesselink, Melvin Lafeber, David Severs, Martijn W. F. van den Hoogen, Michelle A. H. Sonneveld, Christian R. B. Ramakers, Soma Bahmany, Teun van Gelder, Birgit C. P. Koch, Jorie Versmissen
Summary: The study aimed to determine the prevalence of nonadherence to antihypertensive drugs (AHDs) among patients visiting the nephrology and vascular outpatient clinics. Adherence was assessed by measuring drug concentrations in blood, and the overall adherence rate to AHDs was 78.2%. Furthermore, patients after kidney transplant had a higher adherence rate of 85.7%.
JOURNAL OF HYPERTENSION
(2023)
Review
Immunology
G. van der Elst, H. Varol, M. Hermans, C. C. Baan, J. P. Duong-van Huyen, D. A. Hesselink, R. Kramann, M. Rabant, M. E. J. Reinders, J. H. von der Thuesen, T. P. P. van den Bosch, M. C. Clahsen-van Groningen
Summary: Mast cells are innate immune cells that play multiple roles in immune responses. In addition to their involvement in allergies, they also participate in allograft tolerance and rejection by interacting with regulatory T cells, effector T cells, and B cells, and releasing cytokines and other mediators. Mast cell mediators have both pro- and anti-inflammatory actions, but they overall favor pro-fibrotic pathways. Interestingly, they are also considered to have potential protective effects in tissue remodeling post-injury. This manuscript provides an in-depth understanding of the functional diversity of mast cells in kidney transplants, proposing a model that highlights their dual protective and harmful capabilities in this setting.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Transplantation
Hilal Varol, Guus van der Elst, Carla C. Baan, Myrthe van Baardwijk, Dennis A. Hesselink, Jean-Paul Duong van Huyen, Rafael Kramann, Marion Rabant, Thierry P. P. van den Bosch, Marian C. Clahsen-van Groningen
Summary: This study investigated the potential contribution of mast cells (MCs) to minimal inflammatory lesions in kidney transplants (KTx). The results showed that MC number was correlated with post-transplantation time and interstitial fibrosis, but not with transplant function or survival.
TRANSPLANTATION DIRECT
(2023)
Article
Transplantation
Aleixandra Mendoza Rojas, Jeroen G. H. P. Verhoeven, Ronella de Kuiper, Marian C. Clahsen-van Groningen, Karin Boer, Dennis A. Hesselink, Teun van Gelder, Nicole M. van Besouw, Carla C. Baan
Summary: This study validates that a high number of donor-reactive memory T cells before transplantation is associated with the development of acute rejection after transplantation. Furthermore, it demonstrates that the IFN-gamma and IL-21 ELISPOT assays are able to discriminate between patients with acute rejection and patients without acute rejection at the time of biopsy sampling.
TRANSPLANTATION DIRECT
(2023)
Review
Pharmacology & Pharmacy
Suwasin Udomkarnjananun, Thanee Eiamsitrakoon, Brenda C. M. de Winter, Teun van Gelder, Dennis A. Hesselink
Summary: The measurement of whole blood concentration of tacrolimus has been the primary method for therapeutic drug monitoring, but the pharmacologically active fractions are only a small fraction of the measured concentration. Measuring the intracellular tacrolimus concentration may better reflect its pharmacodynamic effects, but conflicting results have been reported. Improvement of the measurement technique and clinical evaluation are needed before its use in clinical practice.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Editorial Material
Immunology
Carla C. Baan, Marlies E. J. Reinders, Dennis A. Hesselink
Article
Medicine, Research & Experimental
Daphne M. Hullegie-Peelen, Hector Tejeda Mora, Dennis A. Hesselink, Eric M. J. Bindels, Thierry P. P. van den Bosch, Marian C. Clahsen-van Groningen, Marjolein Dieterich, Sebastiaan Heidt, Robert C. Minnee, Georges M. G. M. Verjans, Martin J. Hoogduijn, Carla C. Baan
Summary: This study demonstrates the presence of diverse populations of tissue-resident lymphocytes (TRLs) in kidney transplants, including innate, innate-like, and adaptive TRLs. Chimerism of donor and recipient cells is common in kidney transplants and is present in all types of tissue-resident memory T cells. These cells may contribute to local protection against viral pathogens.
Meeting Abstract
Peripheral Vascular Disease
Laura E. J. Peeters, Dennis A. Hesselink, Brenda C. M. de Winter, Melvin Lafeber, David Severs, Martijn W. F. van den Hoogen, Michelle A. H. Sonneveld, Chris R. B. Ramakers, Soma Bahmany, Teun van Gelder, Birgit C. P. Koch, Jorie Versmissen
JOURNAL OF HYPERTENSION
(2023)
Article
Surgery
Lukas K. van Vugt, Marieke van der Zwan, Marian C. Clahsen-van Groningen, Madelon van Agteren, Daphne M. Hullegie-Peelen, Brenda C. M. De Winter, Marlies E. J. Reinders, Pedro Miranda Afonso, Dennis A. Hesselink
Summary: Alemtuzumab is an effective treatment for severe kidney transplant rejection, but it results in long-lasting lymphocyte depletion and is associated with frequent infections and worse patient survival outcomes.
TRANSPLANT INTERNATIONAL
(2023)
