Article
Pharmacology & Pharmacy
Stef Schouwenburg, Enno D. Wildschut, M. de Hoog, Birgit C. P. Koch, Alan Abdulla
Summary: The EXPAT Kids study is designed to analyze whether current empiric dosing regimens of frequently used beta-lactam antibiotics achieve defined therapeutic target concentrations in PICU patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Infectious Diseases
Jing Zhou, Li Jiang, Zhi-Ling Zhang, Zhao-Rui Wang, Yan-Xiu Zhang, Xu Lin, Bo-Hao Tang, Bu-Fan Yao, Zi-Xuan Guo, Jing-Jing Yang, John Van den Anker, Yue-E Wu, Wei Zhao
Summary: This study aims to describe the pharmacokinetic characteristics of mezlocillin in neonates and young infants, and propose the optimal dosing regimen based on the population pharmacokinetic model of mezlocillin. The results showed that a two-compartment model with first-order elimination can be used to describe the population pharmacokinetics of mezlocillin, and postmenstrual age, current weight, and serum creatinine concentration are the most important covariates.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Immunology
Sarah Jane Commander, Daniel K. Benjamin, Huali Wu, Elizabeth J. Thompson, Morgan Lane, Reese H. Clark, Rachel G. Greenberg, Christoph P. Hornik
Summary: This study aimed to investigate the prevalence of seizures in infants after receiving metronidazole and explore the association between metronidazole dose and exposure duration and the occurrence of seizures. The results showed that longer metronidazole exposure and higher cumulative exposure could be associated with increased odds of infant seizures.
PEDIATRIC INFECTIOUS DISEASE JOURNAL
(2023)
Article
Pharmacology & Pharmacy
Hao-Ran Dai, Yun Liu, Ke-Yu Lu, Xin He, Hong-Li Guo, Ya-Hui Hu, Jing Xu, Xuan-Sheng Ding, Feng Chen, Rui Cheng, Zheng Jiao
Summary: This study developed population pharmacokinetic models of caffeine in preterm infants and proposed model-informed precision dosing. Factors such as postnatal age, coadministration with erythromycin, and a specific gene variant were found to impact caffeine concentrations in premature infants. Monte Carlo simulations showed the effects of these factors on caffeine levels under different dosing regimens. These findings offer new insights into caffeine therapy for preterm infants.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Pediatrics
Kaoru Okazaki, Noriyasu Fukuoka, Toru Kuboi, Jun Unemoto, Masatoshi Kondo, Takashi Kusaka, Susumu Itoh
Summary: This study investigated the clearance rate of furosemide after intravenous injection in very preterm neonates, and found that serum creatinine level is the key factor influencing drug clearance.
PEDIATRICS INTERNATIONAL
(2022)
Article
Microbiology
Praneeth Jarugula, Ayse Akcan-Arikan, Flor Munoz-Rivas, Brady S. Moffett, Vijay Ivaturi, Danielle Rios
Summary: This study aimed to determine the optimal vancomycin starting dose regimens in infants <= 180 days of age to achieve the highest probability of target attainment with AUC(24) of >= 400. It also examined the relationship between serum creatinine and vancomycin clearance in neonates.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Olga I. Butranova, Elena A. Ushkalova, Sergey K. Zyryanov, Mikhail S. Chenkurov
Summary: Neonatal infections, particularly neonatal sepsis, contribute significantly to mortality rates and require empiric antibiotic therapy. However, the rise of antibacterial resistance has led to the use of antibiotics from higher-risk groups associated with less clinical experience. Choosing the proper dosing regimen is complicated in neonates due to the high variability in the maturation of organ systems. The developmental changes of pharmacokinetic parameters in preterm and full-term infants should be considered in neonatal intensive care units.
Article
Chemistry, Multidisciplinary
Sho Tashiro, Kazuaki Taguchi, Yuki Enoki, Kazuaki Matsumoto
Summary: The PK/PD characteristics of metronidazole (MNZ) in Clostridioides difficile infection (CDI) were determined using a fecal PK/PD analysis model. The results showed a concentration-dependent bactericidal activity of MNZ, with a target value of fecal AUC(24)/MIC >= 188 for CDI treatment. These findings contribute to the effective clinical use of MNZ.
PHARMACEUTICAL RESEARCH
(2023)
Article
Pediatrics
Aline G. J. Engbers, Robert B. Flint, Swantje Voeller, Irwin Reiss, Kian D. Liem, Jan-Willem C. Alffenaar, Dick Tibboel, Sinno Simons, Catherijne A. J. Knibbe, Roger J. Bruggemann
Summary: A population pharmacokinetic study on fluconazole in preterm neonates was performed to optimize dosing based on patient characteristics. The study found that clearance of fluconazole is best predicted by body weight and serum creatinine concentration, and dose adjustments are required for therapeutic target attainment.
ARCHIVES OF DISEASE IN CHILDHOOD
(2022)
Article
Pharmacology & Pharmacy
Bin Du, Yue Zhou, Bo-Hao Tang, Yue-E Wu, Xin-Mei Yang, Hai-Yan Shi, Bu-Fan Yao, Guo-Xiang Hao, Dian-Ping You, John van den Anker, Yi Zheng, Wei Zhao
Summary: In this study, a population pharmacokinetic model of cefathiamidine for infants with ARC was developed, with weight and age found to influence drug kinetics. Recommended dosing regimens based on PTA were provided for optimal treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Manna Semere Gebreyesus, Eric H. Decloedt, Catherine A. Cluver, Nicole G. M. Hunfeld, Holmfridur Helgadottir, Einar S. Bjornsson, Roeland E. Wasmann, Paolo Denti
Summary: This study investigated the pharmacokinetics of esomeprazole during pregnancy and found that the clearance rate in pregnant participants was lower compared to non-pregnant due to the inhibition of CYP2C19.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Microbiology
Mohammad H. Alshaer, Sylvain Goutelle, Barbara A. Santevecchi, Bethany R. Shoulders, Veena Venugopalan, Kartikeya Cherabuddi, Jiajun Liu, Patrick J. Kiel, Jason A. Roberts, Fekade Bruck Sime, Marc H. Scheetz, Michael N. Neely, Charles A. Peloquin
Summary: In this study, a cefepime model for clinical application was developed and validated. The model was integrated in a precision dosing tool with a median concentration prediction bias of 4%. The optimal initial dose algorithm was provided.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Medicine, General & Internal
Theodore Dassios, Emma E. Williams, Christopher Harris, Anne Greenough
Summary: In this study, cluster analysis is used to identify discrete phenotypic groups of extremely preterm infants, and it is found that these groups have different neonatal outcomes.
Article
Multidisciplinary Sciences
Jennifer Lee, Jinjin Cai, Fuhai Li, Zachary A. Vesoulis
Summary: This study investigates the mortality risk of extremely preterm infants and finds that using a random forest model can better predict mortality risk, surpassing traditional clinical prediction models.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Sergey Zyryanov, Irina Bondareva, Olga Butranova, Alexandra Kazanova
Summary: This study aimed to determine the population pharmacokinetic parameters of meropenem in preterm infants and evaluate the pharmacodynamic indices and covariates affecting pharmacokinetics. Analysis of demographic, clinical, and therapeutic drug monitoring data from 66 preterm newborns revealed that the median values for elimination rate and volume of distribution of meropenem were 0.31 1/h and 1.2 L respectively, and the median values for total clearance and elimination half-life were 0.22 L/h/kg and 2.33 h. Individualized Bayesian posterior models improved prediction quality compared to the population model.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Infectious Diseases
Craig Sykes, Brian Van Horne, Justin Jones, Angela D. M. Kashuba, Gregory Gatto, Ariane Van der Straten, Leah Johnson, Mackenzie L. Cottrell
Summary: This study investigated the phosphorylation of EFdA across commonly used animal species in drug development and found that EFdA-tp concentrations were lower in all species compared to humans. Additionally, PBMCs from rhesus macaques and dogs exhibited significantly higher dATP concentrations compared to human PBMCs.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Editorial Material
Immunology
Charles W. Flexner, Angela Kashuba
CURRENT OPINION IN HIV AND AIDS
(2022)
Article
Gastroenterology & Hepatology
Tahrima Kayes, Harry Crane, Allison Symonds, Julie Dumond, Mackenzie Cottrell, Julia Di Girolamo, Sicha Manandhar, Tien Huey Lim, Edward Gane, Angela Kashuba, Miriam T. Levy
Summary: This study evaluated the pharmacokinetics of tenofovir alafenamide (TAF) and tenofovir (TFV) in breast milk and found that the concentrations of TAF and TFV were low, with negligible exposure to breastfeeding infants. These findings support the use of TAF to prevent mother-to-child transmission of chronic hepatitis B.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Microbiology
Joseph N. Mwangi, William M. Gilliland, Nicole White, Craig Sykes, Amanda Poliseno, Kelly A. Knudtson, Lisa Hightow-Weidman, Angela D. M. Kashuba, Elias P. Rosen
Summary: A new noninvasive method for measuring daily adherence to antiretroviral regimens using hair strands has been developed, offering a potential for better understanding of individual adherence behaviors and short-term changes.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Sara N. Salerno, Edmund Capparelli, Helen McIlleron, Jacqueline G. Gerhart, Julie B. Dumond, Angela D. M. Kashuba, Paolo Denti, Daniel Gonzalez
Summary: This study used physiologically based pharmacokinetic modeling to optimize the dosage of LPV/RTV in children with HIV/TB co-infection, achieving therapeutic levels of LPV trough concentrations.
Article
Immunology
Elias P. Rosen, Claire Deleage, Nicole White, Craig Sykes, Catherine Brands, Lourdes Adamson, Paul Luciw, Jacob D. Estes, Angela D. M. Kashuba
Summary: The study revealed heterogeneous distribution of ARVs in lymph nodes, with lower penetration of ARVs in infected animals compared to healthy animals, but no increase in collagen deposition was found. Some areas of LN tissue were not exposed to detectable ARVs, and regions associated with B cell follicles showed a significant reduction in drug concentration. Nearest neighbour analysis showed that a small percentage of target cells and cell-associated vRNA were not directly contiguous to any drug at concentrations above the IC50 value.
JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
(2022)
Article
Pharmacology & Pharmacy
Jordan B. Joiner, Jasmine L. King, Roopali Shrivastava, Sarah Anne Howard, Mackenzie L. Cottrell, Angela D. M. Kashuba, Paul A. Dayton, Soumya Rahima Benhabbour
Summary: This study investigated the effects of formulation parameters on the in situ forming implant (ISFI) drug delivery system using ultrasound imaging and pharmacokinetics (PK) in mice. The results showed that drug loading extended the degradation time of ISFIs, and there was no statistical difference in drug exposure with different administration routes and injection numbers.
Article
Multidisciplinary Sciences
Carolina Herrera, Mackenzie L. Cottrell, John Prybylski, Angela D. M. Kashuba, Ronald S. Veazey, Javier Garcia-Perez, Natalia Olejniczak, Clare F. McCoy, Paul Ziprin, Nicola Richardson-Harman, Jose Alcami, Karl R. Malcolm, Robin J. Shattock
Summary: The utility of non-human primates in evaluating antiretroviral drugs for HIV treatment and prevention is questionable due to pharmacological differences between humans and macaques. We developed an ex vivo model using tissue explants to identify differences in drug efficacy between the two species. Our results showed that high concentrations of tenofovir and maraviroc predicted anti-viral efficacy, with greater inhibitory potency observed in macaques compared to humans.
Article
Public, Environmental & Occupational Health
John T. Mitchell, Charles M. Burns, Breyah Atkinson, Mackenzie Cottrell, Justin K. Frye, Mehri S. McKellar, Angela D. M. Kashuba, F. Joseph McClernon, Nwora Lance Okeke
Summary: Oral HIV PrEP is effective but often lacks adherence, especially in high-risk groups like Black MSM. The study found that the gamified mobile health intervention mSMART improved PrEP adherence in Black MSM, highlighting the need for future efficacy trials to further validate its effectiveness.
Correction
Public, Environmental & Occupational Health
John T. Mitchell, Charles M. Burns, Breyah Atkinson, Mackenzie Cottrell, Justin K. Frye, Mehri S. McKellar, Angela D. M. Kashuba, F. Joseph McClernon, Nwora Lance Okeke
Article
Pharmacology & Pharmacy
Aaron S. S. Devanathan, Julie B. B. Dumond, Daijha J. C. Anderson, Kristen Moody, Amanda J. J. Poliseno, Amanda P. P. Schauer, Craig Sykes, Cynthia L. L. Gay, Elias P. P. Rosen, Angela D. M. Kashuba, Mackenzie L. L. Cottrell
Summary: Tenofovir diphosphate (TFVdp), an active metabolite of oral HIV pre-exposure prophylaxis (PrEP), is measured in dried blood spots (DBS) to estimate adherence. However, the long half-life of TFVdp in whole blood may lead to misclassification after a change in adherence. Emtricitabine triphosphate (FTCtp), another metabolite of PrEP, has a shorter half-life in whole blood, but adherence thresholds are undefined. This study demonstrates the need for FTCtp to estimate recent adherence and the importance of individualized interpretation for event-driven PrEP adherence monitoring.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Medicine, General & Internal
Jennifer M. Zerbato, Anchalee Avihingsanon, Kasha P. Singh, Wei Zhao, Claire Deleage, Elias Rosen, Mackenzie L. Cottrell, Ajantha Rhodes, Ashanti Dantanarayana, Carolin Tumpach, Surekha Tennakoon, Megan Crane, David J. Price, Sabine Braat, Hugh Mason, Michael Roche, Angela D. M. Kashuba, Peter A. Revill, Jennifer Audsley, Sharon R. Lewin
Summary: This study investigated the persistence of HIV infection in the liver during antiretroviral therapy (ART). The study found that prior to ART, HIV DNA and RNA were detected in the liver tissue of some participants. After ART, low levels of HIV DNA were still observed in the liver tissue of some participants. This suggests that HIV may persist in the liver during ART and requires further investigation.
Article
Multidisciplinary Sciences
Isabella C. Young, Ivana Massud, Mackenzie L. Cottrell, Roopali Shrivastava, Panita Maturavongsadit, Alka Prasher, Andres Wong-Sam, Chuong Dinh, Tiancheng Edwards, Victoria Mrotz, James Mitchell, Josilene Nascimento Seixas, Aryani Pallerla, Allison Thorson, Amanda Schauer, Craig Sykes, Gabriela de la Cruz, Stephanie A. Montgomery, Angela D. M. Kashuba, Walid Heneine, Charles W. Dobard, Martina Kovarova, J. Victor Garcia, J. Gerardo Garcia-Lerma, S. Rahima Benhabbour
Summary: The authors developed an injectable, biodegradable, and removable in-situ forming implant (ISFI) that can release cabotegravir (CAB) for more than 6 months, protecting against HIV for an extended period. The implant was well-tolerated and provided complete protection against multiple rectal SHIV challenges in female macaques. This study supports the clinical use of CAB ISFIs for ultra-long-acting HIV pre-exposure prophylaxis (PrEP) in humans.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Yury Desyaterik, Joseph N. Mwangi, MaryPeace McRae, Austin M. Jones, Angela D. M. Kashuba, Elias P. Rosen
Summary: In this study, we developed a method to analyze the spatial distributions of morphine and abacavir in mouse brain tissue using IR-MALDESI and Q Exactive Plus mass spectrometer. By analyzing different Orbitrap mass spectrometry acquisition modes and evaluating them based on signal abundance and frequency of detection, we achieved higher sensitivity to morphine. Our results showed successful detection of morphine in mouse brain tissue, with the selected ion monitoring mode providing 2.5 times higher sensitivity than the full-scan mode. Furthermore, we found a high correlation between the distributions of morphine and abacavir, with a Pearson correlation coefficient of R = 0.87.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Erick Leung, Mackenzie Cottrell, Craig Sykes, Nicole White, Angela Kashuba, Julie Dumond
Summary: The use of mathematical modeling and simulation can predict outcomes of HIV pre-exposure prophylaxis regimens, aiding in optimizing drug dosage and dosing frequency to mitigate the risk of clinical trial failure.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)