Article
Health Care Sciences & Services
Nicola Personeni, Laura Giordano, Angelica Michelini, Antonio D'Alessio, Antonella Cammarota, Silvia Bozzarelli, Tiziana Pressiani, Maria Giuseppina Prete, Maria Teresa Sandri, Sabine Stioui, Luca Germagnoli, Armando Santoro, Lorenza Rimassa, Rossana Mineri
Summary: This study investigated the impact of UGT1A1 genotyping and genotype-guided dose reductions on the occurrence of severe neutropenia in patients with advanced gastrointestinal cancers. The results show that upfront dose reductions of irinotecan cannot reduce the burden of grade >= 3 neutropenia in homozygous UGT1A1*28 carriers.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Dorina van der Mey, Michael Gerisch, Natalia A. Jungmann, Andreas Kaiser, Kenichi Yoshikawa, Simone Schulz, Martin Radtke, Silvia Lentini
Summary: Molidustat is an oral inhibitor used for the treatment of anemia related to chronic kidney disease by enhancing EPO response to HIF. Glucuronidation of molidustat is predominantly mediated by UGT1A1, and coadministration with UGT1A1 inhibitor atazanavir can increase molidustat exposure and EPO release. However, the combination of molidustat and atazanavir was well tolerated in clinical studies.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2021)
Article
Immunology
David W. Haas, Mahmoud Tareq Abdelwahab, Stijn W. van Beek, Paxton Baker, Gary Maartens, Yuki Bradford, Marylyn D. Ritchie, Sean Wasserman, Graeme Meintjes, Karen Beeri, Neel R. Gandhi, Elin M. Svensson, Paolo Denti, James C. M. Brust
Summary: CYP3A5*3 is associated with slower plasma bedaquiline clearance, and the different frequencies of this variation among populations may explain the faster clearance in individuals of African ancestry.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Immunology
Jeremiah D. Momper, Jiajia Wang, Alice Stek, David E. Shapiro, Kathleen M. Powis, Mary E. Paul, Martina L. Badell, Renee Browning, Nahida Chakhtoura, Kayla Denson, Kittipong Rungruengthanakit, Kathleen George, Edmund Capparelli, Mark Mirochnick, Brookie M. Best, P. Impaact
Summary: This study evaluated the pharmacokinetics of atazanavir and cobicistat during pregnancy and found that standard dosing resulted in lower exposure, which may increase the risk of virologic failure and perinatal transmission.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2022)
Article
Pharmacology & Pharmacy
Daniela Poblete, Fernando Bernal, Gabriel Llull, Sebastian Archiles, Patricia Vasquez, Leonardo Chanqueo, Nicole Soto, Maria A. Lavanderos, Luis A. Quinones, Nelson M. Varela
Summary: UGT1A1*28 and CYP2B6 c.516G>T genetic polymorphisms were found to be associated with moderate-to-severe hyperbilirubinemia and CNS toxicity in HIV patients treated with ATV or EFV at San Juan de Dios Hospital in Chile. Larger prospective studies are needed to validate these associations in the population.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Shaoxing Guan, Xi Chen, Youhao Chen, Guohui Wan, Qibiao Su, Heng Liang, Yunpeng Yang, Wenfeng Fang, Yan Huang, Hongyun Zhao, Wei Zhuang, Shu Liu, Fei Wang, Wei Feng, Xiaoxu Zhang, Min Huang, Xueding Wang, Li Zhang
Summary: This study investigated the effective predictor and alternative treatment for hepatotoxicity induced by gefitinib in non-small cell lung cancer patients using a multi-omics approach. It was found that the rs4946935 AA variant in the FOXO3 gene was associated with a higher risk of hepatotoxicity, particularly at high gefitinib concentrations. Functional experiments revealed that the rs4946935_Lambda variant impaired the expression of FOXO3, leading to an imbalance in autophagy and contributing to gefitinib-induced liver injury. In contrast, liver injury induced by erlotinib was independent of the FOXO3 variant and expression levels. FOXO3 mutation serves as an effective predictor for gefitinib-induced hepatotoxicity, and erlotinib may be a suitable and well-tolerated treatment option for patients carrying the rs4946935 AA variant.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Pharmacology & Pharmacy
Noppaket Singkham, Anchalee Avihingsanon, Richard C. Brundage, Angela K. Birnbaum, Narukjaporn Thammajaruk, Kiat Ruxrungtham, Torsak Bunupuradah, Sasisopin Kiertiburanakul, Ploenchan Chetchotisakd, Baralee Punyawudho
Summary: This study aimed to investigate the optimal dose of RTV-boosted ATV for Thai adult HIV-infected patients. Results showed that CYP3A5 6986A > G and female gender were associated with decreased ATV clearance in Thai patients. Simulations supported that a reduced dose of ATV/RTV was sufficient to achieve the target concentration for the Thai population.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Banaz Abbas, Nagwa A. Sabri, Amal A. El-Khouly
Summary: The study aimed to investigate the effects of food and selected single nucleotide polymorphisms in the UGT2B7 gene on the pharmacokinetics and pharmacodynamics behavior of indapamide. The results showed that food had a modest impact on the maximum concentration and absorption time of indapamide, while genetic variations in the UGT2B7 gene had no significant impact on the pharmacokinetic parameters. It was concluded that food had a moderate effect on the pharmacokinetics, but there were no significant differences in safety and efficacy.
Article
Pharmacology & Pharmacy
Toshinori Hirai, Yoshihiko Morikawa, Ritsuki Onishi, Yusuke Nakatani, Kouhei Nishikawa, Takahiro Inoue, Takuya Iwamoto
Summary: This study evaluated the relationship between HbA1c levels and the pharmacokinetics of controlled-release tacrolimus. The results showed that HbA1c levels and CYP3A5 genotypes may affect tacrolimus blood concentrations after 6 months post-kidney transplantation.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Chang-Keun Cho, Ji-Young Byeon, Pureum Kang, Hye-Jung Park, Eunvin Ko, Chou Yen Mu, Choon-Gon Jang, Seok-Yong Lee, Yun Jeong Lee
Summary: Tolperisone hydrochloride is a centrally-acting muscle relaxant that is used to relieve spasticities and muscle spasms. The pharmacokinetics of tolperisone are significantly affected by the genetic polymorphism of CYP2C19, resulting in higher plasma concentration and lower clearance values in individuals with the CYP2C19PM genotype.
ARCHIVES OF PHARMACAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Chang-Keun Cho, Ji-Young Byeon, Pureum Kang, Jung-In Park, Choon-Gon Jang, Seok-Yong Lee, Chang-Ik Choi, Jung-Woo Bae, Yun Jeong Lee
Summary: Tolperisone, a muscle relaxant used for post-stroke spasticity, exhibits wide interindividual pharmacokinetic variability due to its metabolism by CYP2D6. CYP2D6*10 genotype has a significant impact on the pharmacokinetics of tolperisone. Higher C-max and lower CL/F values were observed in individuals with CYP2D6*10 allele, leading to increased AUC for tolperisone. Factors other than CYP2D6 may also contribute to the wide variability in tolperisone pharmacokinetics.
ARCHIVES OF PHARMACAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Ling Cong, Zirui Wan, Pengfei Li, Dan Liu, Jiuming He, Zhuoling An, Lihong Liu
Summary: This study developed a means of predicting response to olanzapine by combining pharmacokinetics, pharmacometabonomics, and genetic polymorphism. They identified key genes and metabolic pathways related to the effects of olanzapine, and discovered biomarkers for predicting its efficacy.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
M. C. Kravetz, M. S. Viola, J. Prenz, M. Curi, G. F. Bramuglia, S. Tenembaum
Summary: This case report presents a female infant with epilepsy of infancy with migrating focal seizures (EIMFS) who carries a genetic variant in KCNT1 gene and showed poor response to antiepileptic drugs. Therapeutic drug monitoring was essential for establishing individual therapeutic range and avoiding toxicity of quinidine, which was added to the treatment regimen along with other antiepileptic drugs. Precision Medicine using Next Generation Sequencing and TDM was effective in diagnosing and selecting targeted therapy for the patient, highlighting the importance of personalized treatment in patients with genetic epilepsy.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Kalpna Jakhar, Swetha Vaishnavi, Prabhsimran Kaur, Paramdeep Singh, Anjana Munshi
Summary: This review discusses the role and influencing factors of GLP-1RA drugs in the treatment of type 2 diabetes, as well as information on their pharmacokinetics and pharmacodynamics.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Catalina Mares, Ana-Maria Udrea, Nicoleta Anca Sutan, Speranta Avram
Summary: This study isolated chemical compounds from extracts of three Ranunculaceae species and analyzed them from a bioinformatics perspective. The identified compounds were alkaloids and phenols, obtained through microwave-assisted extraction and ultrasound-assisted extraction. The quantification of pharmacokinetics, pharmacogenomics, and pharmacodynamics helped identify the biologically active compounds. The compounds showed good absorption at the intestinal level and high permeability at the level of the central nervous system for alkaloids. Additionally, alkaloids were found to influence tumor sensitivity and treatment effectiveness, and the compounds from these species bound to carbonic anhydrase and aldose reductase.
Article
Genetics & Heredity
Christian Hammer, Martin Begemann, Paul J. McLaren, Istvan Bartha, Angelika Michel, Beate Klose, Corinna Schmitt, Tim Waterboer, Michael Pawlita, Thomas F. Schulz, Hannelore Ehrenreich, Jacques Fellay
AMERICAN JOURNAL OF HUMAN GENETICS
(2015)
Article
Immunology
Sulggi A. Lee, Joel A. Mefford, Yong Huang, John S. Witte, Jeffrey N. Martin, David W. Haas, Paul J. Mclaren, Taisei Mushiroda, Michiaki Kubo, Helen Byakwaga, Peter W. Hunt, Deanna L. Kroetz
Article
Microbiology
Christian Krapp, Dominik Hotter, Ali Gawanbacht, Paul J. McLaren, Silvia F. Kluge, Christina M. Stuerzel, Katharina Mack, Elisabeth Reith, Susanne Engelhart, Angela Ciuffi, Veit Hornung, Daniel Sauter, Amalio Telenti, Frank Kirchhoff
CELL HOST & MICROBE
(2016)
Article
Genetics & Heredity
Paul J. McLaren, Jean Louis Raisaro, Manel Aouri, Margalida Rotger, Erman Ayday, Istvan Bartha, Maria B. Delgado, Yannick Vallet, Huldrych F. Gunthard, Matthias Cavassini, Hansjakob Furrer, Thanh Doco-Lecompte, Catia Marzolini, Patrick Schmid, Caroline Di Benedetto, Laurent A. Decosterd, Jacques Fellay, Jean-Pierre Hubaux, Amalio Telenti
GENETICS IN MEDICINE
(2016)
Article
Multidisciplinary Sciences
Javier Martinez-Picado, Paul J. McLaren, Itziar Erkizia, Maureen P. Martin, Susana Benet, Margalida Rotger, Judith Dalmau, Dan Ouchi, Steven M. Wolinsky, Sudhir Penugonda, Huldrych F. Gunthard, Jacques Fellay, Mary Carrington, Nuria Izquierdo-Useros, Amalio Telenti
NATURE COMMUNICATIONS
(2016)
Article
Immunology
Samira Asgari, Paul J. McLaren, Jane Peake, Melanie Wong, Richard Wong, Istvan Bartha, Joshua R. Francis, Katia Abarca, Kyra A. Gelderman, Philipp Agyeman, Christoph Aebi, Christoph Berger, Jacques Fellay, Luregn J. Schlapbach
FRONTIERS IN IMMUNOLOGY
(2016)
Article
Biochemical Research Methods
Istvan Bartha, Paul J. McLaren, Chanson Brumme, Richard Harrigan, Amalio Telenti, Jacques Fellay
PLOS COMPUTATIONAL BIOLOGY
(2017)
Article
Multidisciplinary Sciences
Jatin Arora, Paul J. McLare, Nimisha Chaturvedi, Mary Carrington, Jacques Fellay, Tobias L. Lenz
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Review
Genetics & Heredity
Shanelle N. Gingras, David Tang, Jeffrey Tuff, Paul J. McLaren
Review
Genetics & Heredity
Paul J. McLaren, Jacques Fellay
Summary: Research has shown how HIV infection affects human immunity and how human genetic variation impacts our response to HIV. Studies have also found that HIV integrates into the human genome and explored new therapeutic approaches for HIV infection.
NATURE REVIEWS GENETICS
(2021)
Article
Multidisciplinary Sciences
Paul J. J. McLaren, Immacolata Porreca, Gennaro Iaconis, Hoi Ping Mok, Subhankar Mukhopadhyay, Emre Karakoc, Sara Cristinelli, Cristina Pomilla, Istvan Bartha, Christian W. W. Thorball, Riley H. H. Tough, Paolo Angelino, Cher S. S. Kiar, Tommy Carstensen, Segun Fatumo, Tarryn Porter, Isobel Jarvis, William C. C. Skarnes, Andrew Bassett, Marianne K. K. DeGorter, Mohana Prasad Sathya Moorthy, Jeffrey F. F. Tuff, Eun-Young Kim, Miriam Walter, Lacy M. M. Simons, Arman Bashirova, Susan Buchbinder, Mary Carrington, Andrea Cossarizza, Andrea De Luca, James J. J. Goedert, David B. B. Goldstein, David W. W. Haas, Joshua T. T. Herbeck, Eric O. O. Johnson, Pontiano Kaleebu, William Kilembe, Gregory D. D. Kirk, Neeltje A. A. Kootstra, Alex H. H. Kral, Olivier Lambotte, Ma Luo, Simon Mallal, Javier Martinez-Picado, Laurence Meyer, Jose M. Miro, Pravi Moodley, Ayesha A. A. Motala, James I. I. Mullins, Kireem Nam, Niels Obel, Fraser Pirie, Francis A. A. Plummer, Guido Poli, Matthew A. A. Price, Andri Rauch, Ioannis Theodorou, Alexandra Trkola, Bruce D. D. Walker, Cheryl A. A. Winkler, Jean-Francois Zagury, Stephen B. B. Montgomery, Angela Ciuffi, Judd F. F. Hultquist, Steven M. M. Wolinsky, Gordon Dougan, Andrew M. L. Lever, Deepti Gurdasani, Harriet Groom, Manjinder S. S. Sandhu, Jacques Fellay
Summary: This study identified a previously undescribed association signal on chromosome 1 that is specific to African populations and is associated with lower set-point viral load in individuals living with HIV-1. Experimental studies showed that the gene CHD1L, which is involved in DNA repair, may play a role in limiting HIV-1 replication.
Correction
Multidisciplinary Sciences
Paul J. McLaren, Immacolata Porreca, Gennaro Iaconis, Hoi Ping Mok, Subhankar Mukhopadhyay, Emre Karakoc, Sara Cristinelli, Cristina Pomilla, Istvan Bartha, Christian W. Thorball, Riley H. Tough, Paolo Angelino, Cher S. Kiar, Tommy Carstensen, Segun Fatumo, Tarryn Porter, Isobel Jarvis, William C. Skarnes, Andrew Bassett, Marianne K. DeGorter, Mohana Prasad Sathya Moorthy, Jeffrey F. Tuff, Eun-Young Kim, Miriam Walter, Lacy M. Simons, Arman Bashirova, Susan Buchbinder, Mary Carrington, Andrea Cossarizza, Andrea De Luca, James J. Goedert, David B. Goldstein, David W. Haas, Joshua T. Herbeck, Eric O. Johnson, Pontiano Kaleebu, William Kilembe, Gregory D. Kirk, Neeltje A. Kootstra, Alex H. Kral, Olivier Lambotte, Ma Luo, Simon Mallal, Javier Martinez-Picado, Laurence Meyer, Jose M. Miro, Pravi Moodley, Ayesha A. Motala, James I. Mullins, Kireem Nam, Niels Obel, Fraser Pirie, Francis A. Plummer, Guido Poli, Matthew A. Price, Andri Rauch, Ioannis Theodorou, Alexandra Trkola, Bruce D. Walker, Cheryl A. Winkler, Jean-Francois Zagury, Stephen B. Montgomery, Angela Ciuffi, Judd F. Hultquist, Steven M. Wolinsky, Gordon Dougan, Andrew M. L. Lever, Deepti Gurdasani, Harriet Groom, Manjinder S. Sandhu, Jacques Fellay
Article
Genetics & Heredity
Razan Abujaber, Patrick R. Shea, Paul J. McLaren, Shabir Lakhi, Jill Gilmour, Susan Allen, Jacques Fellay, Edward J. Hollox
ANNALS OF HUMAN GENETICS
(2017)
Article
Biochemistry & Molecular Biology
Quinlan Richert, Adriana Trajtman, Luisa Arroyave, Julia Toews, Marissa Becker, Ken Kasper, Paul McLaren, Zulma Rueda, Yoav Keynan
Article
Genetics & Heredity
F. David Carmona, Augusto Vaglio, Sarah L. Mackie, Jose Hernandez-Rodriguez, Paul A. Monach, Santos Castaneda, Roser Solans, Inmaculada C. Morado, Javier Narvaez, Marc Ramentol-Sintas, Colin T. Pease, Bhaskar Dasgupta, Richard Watts, Nader Khalidi, Carol A. Langford, Steven Ytterberg, Luigi Boiardi, Lorenzo Beretta, Marcello Govoni, Giacomo Emmi, Francesco Bonatti, Marco A. Cimmino, Torsten Witte, Thomas Neumann, Julia Holle, Verena Schoenau, Laurent Sailler, Thomas Papo, Julien Haroche, Alfred Mahr, Luc Mouthon, Oyvind Molberg, Andreas P. Diamantopoulos, Alexandre Voskuyl, Elisabeth Brouwer, Thomas Daikeler, Christoph T. Berger, Eamonn S. Molloy, Lorraine O'Neill, Daniel Blockmans, Benedicte A. Lie, Paul Mclaren, Timothy J. Vyse, Cisca Wijmenga, Yannick Allanore, Bobby P. C. Koeleman, Jennifer H. Barrett, Maria C. Cid, Carlo Salvarani, Peter A. Merkel, Ann W. Morgan, Miguel A. Gonzalez-Gay, Javier Martin
AMERICAN JOURNAL OF HUMAN GENETICS
(2017)