Article
Pediatrics
Stephane Personne, Celine Brochot, Paulo Marcelo, Aurelie Corona, Sophie Desmots, Franck Robidel, Anthony Lecomte, Veronique Bach, Florence Zeman
Summary: This study developed a pregnancy physiologically based pharmacokinetic model to characterize fetal permethrin exposure in rats, highlighting the distribution and transfer of permethrin in maternal and fetal tissues, especially in the fetal brain. This work could be applied to estimate prenatal exposure and placental transfer of permethrin in humans using biomonitoring data.
FRONTIERS IN PEDIATRICS
(2021)
Article
Pediatrics
Babajide Shenkoya, Shakir Atoyebi, Ibrahim Eniayewu, Abdulafeez Akinloye, Adeniyi Olagunju
Summary: Pregnancy-induced changes in pharmacokinetics of antiretrovirals can impact drug exposure in pregnant women and the fetal compartment. Limited knowledge about ARV exposure in lymphoid tissues and fetal plasma poses challenges in ensuring virological suppression during pregnancy. The study demonstrates how certain ARVs penetrate lymphoid tissues and the fetal compartment, highlighting the importance of adequate drug exposure for preventing mother-to-child transmission risk.
FRONTIERS IN PEDIATRICS
(2021)
Article
Pediatrics
Udoamaka Ezuruike, Alexander Blenkinsop, Amita Pansari, Khaled Abduljalil
Summary: Accurate prediction of fetal exposure to drugs excreted by the kidney requires considering the time-varying renal function parameters. This study collected and integrated data on fetal urinary production rate (FUPR) and creatinine measured at different gestational ages, and compared the predicted fetal glomerular filtration rate (GFR) with neonatal values. The results showed that 3D ultrasound methods yielded higher estimates of FUPR compared to 2D methods, and a power law function accurately captured the change in FUPR with fetal age. The predicted FUPR based on 3D data showed a strong linear relationship with amniotic creatinine concentration, and the predicted fetal GFR values were in good agreement with neonatal values at birth.
FRONTIERS IN PEDIATRICS
(2022)
Article
Pharmacology & Pharmacy
Basile Amice, Harvey Ho, En Zhang, Chris Bullen
Summary: This research report presents a rare physiologically based pharmacokinetic (PBPK) model for the absorption, disposition, metabolism and excretion (ADME) of nicotine and its major metabolite cotinine in pregnant women. The model successfully reproduces the higher clearance rates of nicotine and cotinine in pregnant women compared to non-pregnant women, with simulation results showing temporal profiles for their disposition in organs such as the brain, including nicotine reaching its peak concentration within 2 minutes after intravenous injection. Further pharmacokinetic experiments are needed to refine clearance parameters for individual organs and the fetus.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Physiology
Miguel Sanchez-Polan, Evelia Franco, Cristina Silva-Jose, Javier Gil-Ares, Javier Perez-Tejero, Ruben Barakat, Ignacio Refoyo
Summary: This study analyzed 15 studies on the impact of exercise during pregnancy on prenatal depression and depressive symptoms, finding a negative association between moderate exercise and prenatal depression, while inactive pregnant women had a higher risk of prenatal depression. Therefore, supervised exercise during pregnancy may be beneficial for preventing and reducing prenatal depression and depressive symptoms.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Andre Dallmann, John van den Anker, Homa K. Ahmadzia, Natella Rakhmanina
Summary: According to the 2021 World Health Organization's recommendations, millions of people living with HIV have switched from efavirenz-based to dolutegravir-based antiretroviral therapy. However, pregnant individuals transitioning from efavirenz to dolutegravir may face increased risks of insufficient viral suppression due to drug interactions and hormonal changes during pregnancy. This study developed pharmacokinetic models to simulate the switch from efavirenz to dolutegravir in late pregnancy and found that dolutegravir exposure may be suboptimal during the immediate post-switch period, potentially leading to HIV viremia and resistance.
JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yourdasmine Ali Daoud, Cleo Tebby, Remy Beaudouin, Celine Brochot
Summary: Epidemiological studies have found associations between prenatal exposure to lead and neurodevelopmental effects in young children. To assess internal lead exposure in prenatal life, researchers developed a pregnancy physiologically based pharmacokinetic (p-PBPK) model. The model showed varying levels of lead in the fetus's blood and brain throughout pregnancy, with two peaks at the end of the first and third trimesters. Sensitivity analysis indicated that fetal blood lead levels were affected by the maternal burden of bone lead and fetal bone formation at different stages of pregnancy.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Liang Zheng, Hongyi Yang, Andre Dallmann, Xuehua Jiang, Ling Wang, Wei Hu
Summary: A physiologically based pharmacokinetic (PBPK) model of olanzapine in pregnant women was developed and validated in this study. The model predicted that dose adjustment of olanzapine may not be necessary for pregnant women if effective treatment was achieved before pregnancy and fetal toxicity can be ruled out.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jiarui Chen, Xiang You, Wanhong Wu, Guimu Guo, Rongfang Lin, Meng Ke, Pinfang Huang, Cuihong Lin
Summary: This study developed and validated a physiology-based pharmacokinetic (PBPK) model to predict the plasma concentration changes of levetiracetam in pregnant women and their fetuses, and provided advice for dose adjustment. The predictions showed that the area under the steady-state concentration-time curve for levetiracetam decreased to 83%, 62%, and 67% of baseline values in the first, second, and third trimesters, respectively. Based on the PBPK predictions, the recommended dose of levetiracetam is 1.2, 1.6, and 1.5 times the baseline dose in the first, second, and third trimesters, respectively, not exceeding 4000 mg/day in the third trimester due to fetal safety.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pediatrics
Paola Coppola, Essam Kerwash, Susan Cole
Summary: PBPK modelling is widely used in medicine development and regulatory submissions, especially in studying drug pharmacokinetics during pregnancy. Physiological changes during pregnancy may have potential impact on drug pharmacokinetics, so qualified models are needed to support high-risk decisions.
FRONTIERS IN PEDIATRICS
(2021)
Article
Biochemistry & Molecular Biology
Jorge Lopez-Tello, Zoe Schofield, Raymond Kiu, Matthew J. Dalby, Douwe van Sinderen, Gwenaelle Le Gall, Amanda N. Sferruzzi-Perri, Lindsay J. Hall
Summary: This study demonstrates that the bacterium Bifidobacterium breve UCC2003, a key member of the maternal gut microbiota, modulates maternal body adaptations, placental structure, and nutrient transporter capacity, with implications for fetal metabolism and growth.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Pharmacology & Pharmacy
De-cui Cheng, Yao Su, Feifei Li, Xianming Xu
Summary: This study aimed to investigate the efficiency of insulin on reducing gestational lipid profiles and propose a real-world approach to assist clinicians. The results showed that the use of insulin in the management of gestational hypertriglyceridemia is safe and efficient, and it can improve the outcomes of newborns and mothers.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pediatrics
Nupur Chaphekar, Prerna Dodeja, Imam H. Shaik, Steve Caritis, Raman Venkataramanan
Summary: Pregnancy and the postpartum period can result in changes in drug metabolism and efficacy, leading to potential dosage adjustments. However, limited data on fetal and neonatal drug exposure poses challenges for clinical research. The use of modeling and simulation approaches such as population PK and physiologically based PK modeling has shown promise in guiding drug dosing in these special patient populations.
FRONTIERS IN PEDIATRICS
(2021)
Article
Pharmacology & Pharmacy
Thorsten Braun, Loreen Ehrlich, Wolfgang Henrich, Sebastian Koeppel, Ievgeniia Lomako, Philipp Schwabl, Bettina Liebmann
Summary: The study identified the presence of microplastics (> 50 μm) in placenta and meconium samples from caesarean deliveries, with polyethylene, polypropylene, polystyrene, and polyurethane being the main types detected. However, airborne polyurethane microplastics were also found in the operating room, indicating potential contamination sources. Further research into nano-sized plastics in human tissues is recommended.
Article
Pharmacology & Pharmacy
Sara Bettonte, Mattia Berton, Felix Stader, Manuel Battegay, Catia Marzolini
Summary: Physiologically based pharmacokinetics (PBPK) modelling was used to simulate the switch from efavirenz to intramuscular cabotegravir/rilpivirine (IM CAB/RPV). The simulations showed that IM CAB concentrations slightly decreased during the switch, but remained above the minimal efficacy threshold; IM RPV concentrations also had a modest reduction, but did not put at risk of having suboptimal drug levels.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Letter
Pharmacology & Pharmacy
Steven P. Rannard, Tom O. McDonald, Andrew Owen
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
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)
Article
Pharmacology & Pharmacy
Xuezhi Zhuo, Vito Fodera, Per Larsson, Zarah Schaal, Christel A. S. Bergstrom, Korbinian Lobmann, Aleksei Kabedev
Summary: Our previous work demonstrated that beta-lactoglobulin-stabilized amorphous solid dispersion (ASD) loaded with 70 % indomethacin remains stable for over 12 months. We further investigated the stabilization mechanisms by testing five other drug molecules and using experimental techniques and molecular dynamics simulations. The results showed that steric confinement, hydrogen bonding, and the glass transition temperature of the drug molecule play important roles in stabilizing ASDs with high drug loadings.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Sebastian Schmidt, Ulrike Holzgrabe
Summary: The binding of drugs to plasma proteins, such as human serum albumin (HSA), is crucial for determining pharmacokinetic parameters. This study investigated the enantioselective binding of S- and R-ketamine to HSA. It was found that ketamine has weak affinity to HSA, with no significant differences in binding behavior between the individual enantiomers and the racemate. The aromatic ring and N-methyl group were identified as the most strongly involved structural moieties in the binding of ketamine to HSA.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Yuchen Zhao, Han Wang, Lin Jin, Ziwei Zhang, Lianghu Liu, Mengqi Zhou, Xianzheng Zhang, Lingling Zhang
Summary: Interleukins (ILs) are important for communication between immune cells and non-immune cells, but dysregulation of ILs expression is a characteristic of autoinflammatory diseases. Drugs targeting ILs have significant clinical benefits, but may also cause adverse reactions. Fusion protein technology, with its ability to enhance therapeutic efficacy, has been explored for developing anti-inflammatory drugs. This review discusses the efficacy of fusion protein drugs developed with ILs or their receptors in treating autoinflammatory diseases, highlighting the potential of this technology in future anti-inflammatory drug development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Serena Bertoni, Elena Simone, Stefano Sangiorgi, Beatrice Albertini, Nadia Passerini
Summary: This study investigated the correlation between the structure and release properties of solid lipid microparticles (MPs) with different liquid additives. The additives accelerated the conversion of the unstable alpha-form of tristearin to the stable beta-polymorph and caused structural modifications in the MPs. The presence of additives prolonged the drug release in water and resulted in higher release profiles in biorelevant media. The findings suggest that the release behavior can be influenced by the polymorphism and supramolecular-level structural modification of lipid formulations containing crystal modifiers.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Juulia Jarvinen, Ahmed B. Montaser, Santosh Kumar Adla, Jukka Leppanen, Marko Lehtonen, Kati-Sisko Vellonen, Tuomo Laitinen, Aaro Jalkanen, William F. Elmquist, Juri Timonen, Kristiina M. Huttunen, Jarkko Rautio
Summary: This study attempted to alter the brain distribution pattern of Palbociclib by creating and assessing two novel prodrugs. Although the prodrug design did not significantly improve Palbociclib brain delivery, the study provides valuable insights for future prodrug development and drug delivery strategies targeting specific transporters.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Review
Pharmacology & Pharmacy
Miao Wang, Xinyu Ma, Shiyu Zong, Yaqiong Su, Rui Su, Hong Zhang, Yang Liu, Chunliu Wang, Ye Li
Summary: This article discusses the potential and limitations of nasal administration in central nervous system drug delivery. Nasal gel viscosity can alleviate the impact of nasal mucociliary clearance on drug delivery, and materials such as gellan gum, chitosan, carbomer, cellulose, and poloxamer can be used to prepare nasal gels.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Bjarke Strom Larsen, Eric Kissi, Liebert Parreiras Nogueira, Natalja Genina, Ingunn Tho
Summary: This study investigates the influence of drug load and polymer molecular weight on the structure of 3D printed tablets. The results show that drug load and polymer molecular weight have a significant impact on the porosity and size of the tablets, while the effect of drug load on the total porosity of the tablets is minimal.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Zhentao Qiao, Fuhang Wang, Dongjian Han, Yuansong Zhuang, Qingjiao Jiang, Yi Zhang, Miaomiao Liu, Quanxu An, Zhiwei Wang, Deliang Shen
Summary: In this study, it was demonstrated that periadventitial delivery of rapamycin-fibrin glue (RPM-FG) can inhibit intimal hyperplasia (IH) in a rat carotid artery injury model without compromising re-endothelialization. This provides a promising direction for the future development of a safe, effective, and minimally invasive perivascular drug delivery method to treat vascular disease.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Neele Puhlmann, Rodrigo Vidaurre, Klaus Kuemmerer
Summary: Active pharmaceutical ingredients and their metabolites and transformation products are pollutants that can harm human and environmental health. Designing greener APIs is an effective strategy to address this issue. The drug discovery and development process can incorporate environmental parameters to achieve this design, and this process is highly flexible.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)