Editorial Material
Immunology
David W. Haas, Edward P. Acosta
Summary: The study revealed that slow metabolizers of CYP2B6 experienced a greater decrease in dolutegravir concentration and a longer half-life of efavirenz, leading to prolonged subtherapeutic dolutegravir concentrations in these patients.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Pharmacology & Pharmacy
Xian-min Meng, Zi-ran Li, Xin-yin Zheng, Yi-xi Liu, Wan-jie Niu, Xiao-yan Qiu, Hong-zhou Lu
Summary: The study investigated the impact of gene polymorphisms and non-genetic factors on the variability of efavirenz pharmacokinetics, proposing optimal dose regimens based on CYP2B6 polymorphisms.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Natalia A. Shnayder, Marina M. Petrova, Pavel A. Shesternya, Alina V. Savinova, Elena N. Bochanova, Olga V. Zimnitskaya, Elena A. Pozhilenkova, Regina F. Nasyrova
Summary: DOACs, such as dabigatran, rivaroxaban, apixaban, and edoxaban, are commonly used for thromboembolism prevention in various medical fields. The importance of genetic information for predicting pharmacokinetics and risk in patients receiving anticoagulant therapy is increasingly recognized.
Article
Immunology
Roland van Rensburg, Sam Nightingale, Naeem Brey, Christine H. Albertyn, Tracy A. Kellermann, Jantjie J. Taljaard, Tonya M. Esterhuizen, Phumla Z. Sinxadi, Eric H. Decloedt
Summary: Late-onset efavirenz neurotoxicity syndrome (LENS) is caused by genetic mutations conferring slow metabolizer status of the primary efavirenz-metabolizing enzyme, CYP2B6. Additionally, isoniazid as an inhibitor of the accessory efavirenz-metabolizing enzyme pathway, CYP2A6, and low body weight contribute to LENS development.
CLINICAL INFECTIOUS DISEASES
(2022)
Review
Immunology
Million A. Tegenge, Iftekhar Mahmood, Evi B. Struble, Zuben Sauna
Summary: Pharmacokinetics (PK) studies are crucial for determining safe and effective dosages of both small and large molecule drugs. While PK studies have been conducted for small molecules during pregnancy, there is limited research on macromolecules such as monoclonal and polyclonal antibodies. This review provides an overview of macromolecule drugs and their PK differences compared to small molecules, as well as the physiological changes during pregnancy. Further investigations are needed to fully understand the impact of pregnancy on PK properties of macromolecules.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
David W. Haas, Anthony T. Podany, Yajing Bao, Susan Swindells, Richard E. Chaisson, Noluthando Mwelase, Khuanchai Supparatpinyo, Lerato Mohapi, Amita Gupta, Constance A. Benson, Paxton Baker, Courtney V. Fletcher
Summary: Among HIV-positive individuals receiving efavirenz or nevirapine, and who then initiated rifapentine plus isoniazid in A5279, NAT2 slow acetylators had greater rifapentine and 25-desacetyl rifapentine concentrations, and greater increases from baseline in plasma efavirenz and nevirapine concentrations. These associations are likely mediated by greater isoniazid exposure in NAT2 slow acetylators.
PHARMACOGENETICS AND GENOMICS
(2021)
Article
Pharmacology & Pharmacy
Gonzalo Villapalos-Garcia, Pablo Zubiaur, Marcos Navares-Gomez, Miriam Saiz-Rodriguez, Gina Mejia-Abril, Samuel Martin-Vilchez, Manuel Roman, Dolores Ochoa, Francisco Abad-Santos
Summary: The combination therapy of dutasteride and tamsulosin showed higher drug exposure and metabolism half-life in CYP2D6 poor metabolizers and intermediate metabolizers, while fed volunteers exhibited significantly higher time to peak concentration compared to fasting individuals. Associations were found between dutasteride/CYP3A4, CYP3A5 and tamsulosin/ABCG2, CYP3A5, SLC22A1 genotypes, but no correlation was observed between adverse drug reactions and genotype.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Cinzia Dello Russo, Kathryn Anne Scott, Munir Pirmohamed
Summary: Dimethyl fumarate (DMF) is a first line medication for multiple sclerosis, but concerns have been raised regarding its adverse effects such as lymphopenia. The molecular mechanisms underlying these effects are not well understood, and the relative toxicity of DMF and its metabolite MMF in vivo remains unclear.
PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Health Care Sciences & Services
Maha Ali Alghamdi, Antonino N. Fallica, Nicola Virzi, Prashant Kesharwani, Valeria Pittala, Khaled Greish
Summary: Personalized medicine and nanomedicine are both new concepts in medical practice. Personalized medicine aims to customize therapeutic management based on a patient's personal attributes, while nanomedicine applies nanotechnology advances in medicine for diagnosis and treatment. The integration of these two fields can provide more effective treatment options tailored to individual patients.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Health Care Sciences & Services
Adugna Chala, Birkneh Tilahun Tadesse, Tolossa Eticha Chaka, Jackson Mukonzo, Eliford Ngaimisi Kitabi, Sintayehu Tadesse, Anton Pohanka, Eyasu Makonnen, Eleni Aklillu
Summary: The study found that pre-treatment LDL cholesterol levels and CYP2B6*6 and ABCB1c.3435 C > T genotypes are significantly associated with efavirenz plasma exposure among HIV-infected children. However, the duration of treatment did not have a statistically significant impact on changes in plasma efavirenz exposure due to auto-induction.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Catherine S. Stika, Katherine L. Wisner, Alfred L. George, Michael J. Avram, Katelyn Zumpf, Laura J. Rasmussen-Torvik, Gabrielle A. Mesches, Steve N. Caritis, Raman Venkataramanan, Maged M. Costantine, Holly A. West, Shannon Clark, Jody D. Ciolino
Summary: This study aimed to investigate the pharmacokinetics of sertraline during pregnancy and the impact of pharmacogenetic variability on its elimination. The results showed that the ratio of sertraline concentration to dose decreased during pregnancy and was associated with CYP2C19 activity.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(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
Urology & Nephrology
Nuria Lloberas, Josep M. Grinyo, Helena Colom, Anna Vidal-Alabro, Pere Fontova, Raul Rigo-Bonnin, Ariadna Padro, Oriol Bestard, Edoardo Melilli, Nuria Montero, Ana Coloma, Anna Manonelles, Maria Meneghini, Alex Fava, Joan Torras, Josep M. Cruzado
Summary: This study developed and validated a population pharmacokinetic model for tacrolimus dosing, which was found to be superior to traditional labeling-based dosing in achieving therapeutic targets. The model showed faster attainment of therapeutic levels and reduced dosage adjustments compared to the standard approach.
KIDNEY INTERNATIONAL
(2023)
Article
Pharmacology & Pharmacy
Joao Paulo Ximenez, Anna Beatriz Ribeiro Elias, Glauco Henrique Balthazar Nardotto, Paulo Feijo Barroso, Valdes Roberto Bollela, Vera Lucia Lanchote, Guilherme Suarez-Kurtz
Summary: This study aimed to investigate the influence of pharmacogenetic polymorphisms on efavirenz (EFV) exposure and metabolism in HIV-infected Brazilians. The results showed that there was wide interindividual variation in EFV exposure and disposition, and the genotype for the two CYP2B6 single nucleotide polymorphisms studied explained a significant portion of this variation.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Infectious Diseases
Quanhathai Kaewpoowat, Romanee Chaiwarith, Saowaluck Yasri, Navaporn Worasilchai, Ariya Chindamporn, Thira Sirisanthana, Tim R. Cressey
Summary: This study evaluated the pharmacokinetics of itraconazole capsule and its active metabolite, hydroxyitraconazole, in adults with HIV diagnosed with talaromycosis in an endemic area, and assessed the drug-drug interaction between itraconazole/hydroxyitraconazole and efavirenz. Results showed that concurrent administration of itraconazole capsule with efavirenz significantly reduced the exposures of itraconazole and hydroxyitraconazole. Further evaluation is needed to understand the clinical impact of this drug-drug interaction on talaromycosis treatment or prophylaxis in the era of potent ART.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Letter
Pharmacology & Pharmacy
Steven P. Rannard, Tom O. McDonald, Andrew Owen
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Lauren E. Walker, Richard FitzGerald, Geoffrey Saunders, Rebecca Lyon, Michael Fisher, Karen Martin, Izabela Eberhart, Christie Woods, Sean Ewings, Colin Hale, Rajith K. R. Rajoli, Laura Else, Sujan Dilly-Penchala, Alieu Amara, David G. Lalloo, Michael Jacobs, Henry Pertinez, Parys Hatchard, Robert Waugh, Megan Lawrence, Lucy Johnson, Keira Fines, Helen Reynolds, Timothy Rowland, Rebecca Crook, Emmanuel Okenyi, Kelly Byrne, Pavel Mozgunov, Thomas Jaki, Saye Khoo, Andrew Owen, Gareth Griffiths, Thomas E. Fletcher
Summary: Repurposing the drug nitazoxanide may provide effective antiviral concentrations in COVID-19 patients, with the medication showing good safety and tolerability in healthy adult participants. This has led to the initiation of a phase Ib/IIa study in patients with COVID-19.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Microbiology
Frauke Assmus, Jean-Selim Driouich, Rana Abdelnabi, Laura Vangeel, Franck Touret, Ayorinde Adehin, Palang Chotsiri, Maxime Cochin, Caroline S. Foo, Dirk Jochmans, Seungtaek Kim, Lea Luciani, Gregory Moureau, Soonju Park, Paul-Remi Petit, David Shum, Thanaporn Wattanakul, Birgit Weynand, Laurent Fraisse, Jean-Robert Ioset, Charles E. Mowbray, Andrew Owen, Richard M. Hoglund, Joel Tarning, Xavier de Lamballerie, Antoine Nougairede, Johan Neyts, Peter Sjo, Fanny Escudie, Ivan Scandale, Eric Chatelain
Summary: In the absence of drugs to treat or prevent COVID-19, drug repurposing can be a valuable strategy. However, the lack of clear translational processes and adequate preclinical profiling has hindered the success of repurposed drugs. This study proposes a systematic approach to urgent antiviral drug development, utilizing in vitro, ex vivo, and in vivo models along with pharmacokinetic modeling and simulations. The importance of assessing in vitro and in vivo potency and utilizing pharmacokinetic modeling for compound prioritization is emphasized. A standardized translational drug development platform is advocated to generate preclinical evidence for clinical trials in the context of mild-to-moderate COVID-19.
Article
Genetics & Heredity
Rohan Gurjar, Laura Dickinson, Daniel Carr, Wolfgang Stohr, Stefano Bonora, Andrew Owen, Antonio D'Avolio, Adam Cursley, Nathalie De Castro, Gerd Fatkenheuer, Linos Vandekerckhove, Giovanni Di Perri, Anton Pozniak, Christine Schwimmer, Francois Raffi, Marta Boffito
Summary: This study used nonlinear mixed effects modeling to determine the pharmacokinetic parameters of raltegravir and investigate the influence of demographics and SNPs on its pharmacokinetics and pharmacodynamics. The results showed that demographics and SNPs did not significantly affect the pharmacokinetics of raltegravir, and no significant pharmacokinetic/pharmacodynamic relationships were observed. However, at week 96, UGT1A1*28/*28 was associated with lower virological failure.
PHARMACOGENOMICS JOURNAL
(2023)
Editorial Material
Microbiology
Maxime Hentzien, Andrew Owen, Nathalie Strub-Wourgaft, Carmen Perez-Casas, Marius Troseid, Alexandra Calmy
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Immunology
Rujipas Sirijatuphat, Weerawat Manosuthi, Suvimol Niyomnaitham, Andrew Owen, Katherine Kradangna Copeland, Lantharita Charoenpong, Manoch Rattanasompattikul, Surakameth Mahasirimongkol, Nuanjun Wichukchinda, Kulkanya Chokephaibulkit
Summary: Early treatment with Favipiravir was associated with faster clinical improvement in mild COVID-19 cases without pneumonia.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Immunology
David L. Thomas, Andrew Owen, Jennifer J. Kiser
Summary: In 2019, an estimated 58 million people were living with hepatitis C virus infections worldwide. Long-acting parenteral formulations of HCV treatments could potentially diagnose and cure patients in a single encounter. However, various challenges such as pharmacological, regulatory, patent, and medical obstacles need to be addressed.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Immunology
Nicole C. Ammerman, Eric L. Nuermberger, Andrew Owen, Steve P. Rannard, Caren Freel Meyers, Susan Swindells
Summary: This article provides an overview of the specific considerations and current preclinical advancements related to the development of long-acting technologies for tuberculosis drugs to treat latent infection, including target product profiles, suitability of drugs for long-acting formulations, ongoing research efforts, and translation to clinical studies.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Infectious Diseases
Allan Buzibye, Kara Wools-Kaloustian, Adeniyi Olagunju, Ellon Twinomuhwezi, Constantin Yiannoutsos, Andrew Owen, Megan Neary, Joshua Matovu, Grace Banturaki, Barbara Castelnuovo, Mohammed Lamorde, Saye Khoo, Catriona Waitt, Agnes Kiragga
Summary: This study investigated the association between CYP2B6 polymorphisms and efavirenz drug resistance among women living with HIV who started on antiretroviral therapy during pregnancy and had high viremia during the postpartum period. The results showed that there was no statistically significant difference in efavirenz resistance among different metabolizer genotypes.
AIDS RESEARCH AND THERAPY
(2023)
Article
Chemistry, Applied
Nancy M. Elbaz, Andrew Owen, Steve Rannard, Tom O. McDonald
Summary: This work demonstrates the use of a titration method to produce multilayered coatings on a nanosuspension, enhancing the release behavior and stability of curcumin. The results show that a pH-responsive outer layer delays curcumin release in acidic conditions and facilitates its release in neutral conditions. Increasing the number of layers improves the stability of curcumin in the nanosuspension and reduces its toxicity.
FOOD HYDROCOLLOIDS
(2023)
Article
Virology
Eduardo Gallardo-Toledo, Megan Neary, Joanne Sharp, Joanne Herriott, Edyta Kijak, Chloe Bramwell, Paul Curley, Usman Arshad, Henry Pertinez, Rajith K. R. Rajoli, Anthony Valentijn, Helen Cox, Lee Tatham, Anja Kipar, James P. Stewart, Andrew Owen
Summary: This study investigated the chemoprophylactic and therapeutic efficacy of Pibrentasvir (PIB), Favipiravir (FVP), and Remdesivir (RDV) alone or in combination against SARS-CoV-2. The results showed that RDV alone prevented transmission, while other drugs reduced the viral load after contact transmission. However, no additional benefit was observed when combining FVP or RDV with PIB.
Article
Pharmacology & Pharmacy
Paul Curley, James J. Hobson, Neill J. Liptrott, Edward Makarov, Amer Al-khouja, Lee Tatham, Christopher A. W. David, Helen Box, Megan Neary, Joanne Sharp, Henry Pertinez, David Meyers, Charles Flexner, Caren L. Freel Meyers, Larisa Poluektova, Steve Rannard, Andrew Owen
Summary: The study reports the feasibility and predicted antiviral activity of the semi-solid prodrug nanoparticle (SSPN) long-acting injectable (LAI) formulation for the prevention of HIV infection. Preclinical assessments show that the formulation has a prolonged pharmacokinetic half-life in animal models and can effectively suppress viral loads to prevent and control HIV infection.
Article
Engineering, Biomedical
Edyta Niezabitowska, Dominic M. M. Gray, Eduardo Gallardo-Toledo, Andrew Owen, Steve P. P. Rannard, Tom O. O. McDonald
Summary: Core-shell nanogels consisting of poly(N-isopropylmethacrylamide) core and poly(N-isopropylacrylamide) shell crosslinked with a degradable crosslinker were synthesized. The degradation behavior of these nanogels was characterized using asymmetric flow field flow fractionation coupled with multi-angle and dynamic light scattering. The results revealed slower degradation of the core-shell nanogels compared to their non-core-shell counterparts, possibly due to a higher degree of self-crosslinking reactions in the shell. Majority of the degradation products had molecule weights below 10 kDa, suggesting renal clearance.
JOURNAL OF FUNCTIONAL BIOMATERIALS
(2023)
Article
Medicine, General & Internal
Bozana Obradovic, Owain Roberts, Andrew Owen, Ivana Milosevic, Natasa Milic, Jovan Ranin, Gordana Dragovic
Summary: This study investigates the gene expression of CYP2B6, CYP3A4, and ABCB1 transporters in HIV, HCV, and HIV/HCV co-infected patients, and their potential association with therapy choice and liver damage parameters. The results show that CYP2B6 mRNA levels are significantly increased in co-infected patients, while HIV infection is significantly associated with increased CYP3A4 mRNA levels. A trend towards downregulation of ABCB1 expression is observed in patients using lamivudine.
MEDICINA-LITHUANIA
(2023)
Article
Chemistry, Multidisciplinary
Sam Morris, Mark Long, Alison Savage, Andrew Owen, Steve Rannard, Helen Cauldbeck
Summary: The inherent barrier properties of the skin present significant challenges for the transdermal delivery of drugs. In this study, the ex vivo transdermal permeation and deposition of an anti-malarial prophylactic, atovaquone solid drug nanoformulation, was radiometrically evaluated following the application of a solid microneedle format.
NANOSCALE ADVANCES
(2023)
