Article
Microbiology
Antonin Praet, Laurent Bourguignon, Florence Vetele, Valentine Breant, Charlotte Genestet, Oana Dumitrescu, Anne Doleans-Jordheim, Philippe Reix, Sylvain Goutelle
Summary: This study developed nonparametric population pharmacokinetic (PK) models of tobramycin in children with CF for dosage design and model-guided therapeutic drug monitoring, with a recommended daily dose of 12.5 mg/kg optimizing efficacy and safety targets in most patients as validated through simulations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Pediatrics
Katherine B. Landmesser, Elizabeth B. Autry, Brian M. Gardner, Katherine A. Bosko, Aric Schadler, Robert J. Kuhn
Summary: The study found that both AUC(24) and C-max are relatively accurate predictors of tobramycin efficacy, while multiple daily dosing of IV tobramycin significantly increases the incidence of AKI and should be avoided in patients with CF.
PEDIATRIC PULMONOLOGY
(2021)
Article
Medical Laboratory Technology
Kevin Koloskoff, Daniel J. G. Thirion, Elias Matouk, Amelie Marsot
Summary: This study developed a population pharmacokinetic model and established optimal dosing recommendations for tobramycin in adult patients with cystic fibrosis. The study found that height was more suitable than weight for dosing adjustments in adult cystic fibrosis patients. According to the model, initial doses of tobramycin between 3.4 and 4.4 mg/cm should be recommended for patients with a median height of 164 cm and weight of 55 kg to achieve the target plasma concentrations.
THERAPEUTIC DRUG MONITORING
(2023)
Article
Medical Laboratory Technology
Mehdi El Hassani, Daniel J. G. Thirion, Kevin Koloskoff, Elias Matouk, Chantale Simard, Isabelle Cloutier, Sylvie Pilote, Amelie Marsot
Summary: This study aimed to develop a height-based initial dosing nomogram and evaluate its performance in peak concentration (Cmax) precision relative to standard and fixed dosing. Height-based dosing resulted in significantly less variable-predicted Cmax values than the Cmax values observed in clinical practice and predicted Cmax values obtained from a fixed dose. An initial dosing nomogram was developed to help reduce pharmacokinetic variability in the observed Cmax, which would allow for better clinical outcomes in adult patients with cystic fibrosis.
THERAPEUTIC DRUG MONITORING
(2023)
Article
Pharmacology & Pharmacy
Jeremy Reverchon, Vianney Tuloup, Romain Garreau, Viviane Nave, Sabine Cohen, Philippe Reix, Stephane Durupt, Raphaele Nove-Josserand, Isabelle Durieu, Quitterie Reynaud, Laurent Bourguignon, Sandrine Charles, Sylvain Goutelle
Summary: The study on tobramycin MIPD in adult CF patients showed that MIPD was effective in changing prescribing practice, increasing tobramycin doses without causing renal function impairment.
Article
Microbiology
Venkata K. Yellepeddi, Bryn Lindley, Emi Radetich, Shaun Kumar, Zubin Bhakta, Laurie Leclair, Madison Parrot, David C. Young
Summary: In this study, the pharmacokinetics (PK) of vancomycin in people with cystic fibrosis (PwCF) were characterized using a population PK approach. The study evaluated the probability of target attainment (PTA) for 12 different initial dosing scenarios using comprehensive Monte Carlo simulations. The results provide important guidance for vancomycin dosing in the treatment of pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in PwCF.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Mehdi El Hassani, Chantale Simard, Sylvie Pilote, Isabelle Cloutier, Sara Soufsaf, Amelie Marsot
Summary: External evaluation of tobramycin population pharmacokinetic models showed that the ones by Crass et al. and Alghanem et al. performed satisfactorily in terms of prediction-based diagnostics. Simulation-based evaluations suggested that height-based dosing regimens could be considered in cystic fibrosis patients for individualized dosing.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Michael E. Cloesmeijer, Michiel J. van Esdonk, Anne M. Lynn, Anne Smits, Dick Tibboel, Youssef Daali, Klaus T. Olkkola, Karel Allegaert, Paola Mian
Summary: The study aimed to investigate the enantiomer-specific maturational pharmacokinetics of ketorolac in infants and adults, finding different concentrations and ratios of S- and R-ketorolac between the two populations at identical racemic concentrations.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Chelsea R. Thorn, Cristiane de Souza Carvalho-Wodarz, Justus C. Horstmann, Claus-Michael Lehr, Clive A. Prestidge, Nicky Thomas
Summary: A biomimetic, nanostructured, lipid liquid crystal nanoparticle formulation has been discovered to significantly enhance the efficacy of tobramycin and eradicate Pseudomonas aeruginosa biofilm infections. This formulation improves antibiotic penetration across the biofilm barrier, leading to increased antibiotic concentration at the infection site. The nanoparticle strategy enables lower doses, reduced toxicity, and amplified anti-biofilm activity of the antibiotic.
Article
Microbiology
Kevin J. Downes, Austyn Grim, Laura Shanley, Ronald C. Rubenstein, Athena F. Zuppa, Marc R. Gastonguay
Summary: This study retrospectively analyzed clinical data of children under 5 years old with cystic fibrosis (CF) who were treated with tobramycin for pulmonary exacerbations, and performed pharmacokinetic modeling and simulations. The results showed that once-daily dosing did not achieve all therapeutic goals, but extended-interval dosing regimens may reach therapeutic targets in the majority of young patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Zara Sheikh, Peta Bradbury, Tristan A. Reekie, Michele Pozzoli, Paul D. Robinson, Michael Kassiou, Paul M. Young, Hui Xin Ong, Daniela Traini
Summary: Current study investigated the potential interactions between the anti-inflammatory agent Ibuprofen and CF-approved inhaled antibiotics, revealing differential effects on the antibacterial and anti-inflammatory efficacy of the combinations. The study highlighted the importance of understanding drug-drug interactions and highlighted the inherent anti-inflammatory properties of the antibiotics used in CF treatment.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biophysics
Danielle E. Arnold, Chie Emoto, Tsuyoshi Fukuda, Min Dong, Alexander A. Vinks, Adam Lane, Kelly McIntosh, Lisa Neumeier, Arjan C. Lankester, Federica Achini, Ashley Teusink-Cross, Sharat Chandra, Michael B. Jordan, Adam S. Nelson, Kasiani C. Myers, Stella M. Davies, Parinda A. Mehta, Rebecca A. Marsh
Summary: The study found that a concentration intervention strategy can successfully target a greater proportion of patients into the ideal therapeutic window, but further dose-reduction studies are needed to optimize initial dosing and achieve target attainment in all patients.
BONE MARROW TRANSPLANTATION
(2021)
Article
Chemistry, Medicinal
Shelby Barnett, Julie Errington, Julieann Sludden, David Jamieson, Vianney Poinsignon, Angelo Paci, Gareth J. Veal
Summary: The pharmacokinetics of cyclophosphamide in children under 2 years old showed marked inter-patient variability, but no significant differences were observed between age or weight groups. Contrasting results were noted in drug clearance and metabolism between younger children and older patients, indicating potential differences in dosing protocols and drug responses between these age groups.
Article
Immunology
Shivanthan Shanthikumar, Sarath C. Ranganathan, Richard Saffery, Melanie R. Neeland
Summary: By using high parameter flow cytometry and inflammatory cytokine profiling, the study investigated the immune response in preschool children with CF and healthy controls, revealing pulmonary infiltration of CD66b(+) granulocytes and elevated levels of inflammatory cytokines in CF children. Moreover, the proportions of systemic neutrophils in CF children were positively correlated with age, while CD4 T cells and B cells showed an inverse association with age. This work emphasizes the importance of multiplex immune profiling and advanced analytical pipelines in understanding lung disease mechanisms in childhood.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medical Laboratory Technology
Philip G. Drennan, Yann Thoma, Lucinda Barry, Johan Matthey, Sheila Sivam, Sebastiaan J. van Hal
Summary: The study demonstrates that using Bayesian forecasting with single postinfusion concentrations for assessing AUC(24) is feasible in routine practice, yielding similar exposure estimates to more intensive methods.
THERAPEUTIC DRUG MONITORING
(2021)
Review
Health Care Sciences & Services
Bianca J. Levkovich, Judit Orosz, Gordon Bingham, D. James Cooper, Michael Dooley, Carl Kirkpatrick, Daryl A. Jones
Summary: Medication-related activations accounted for one-fourth of emergency team activations, often occurring early in a patient's admission. One-third of these medication-related activations were potentially preventable, with the most common causes being omission of beta-blockers and clinically inappropriate use of antihypertensive drugs.
BMJ QUALITY & SAFETY
(2023)
Article
Pharmacology & Pharmacy
Ranita Kirubakaran, David W. Uster, Stefanie Hennig, Jane E. Carland, Richard O. Day, Sebastian G. Wicha, Sophie L. Stocker
Summary: A population pharmacokinetic model that considers the tacrolimus-azole antifungal interaction was developed for guiding tacrolimus dosing in heart transplant recipients.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
George S. Q. Tan, Erica K. Sloan, Pete Lambert, Carl M. J. Kirkpatrick, Jenni Ilomaki
Summary: The use of real-world data in drug repurposing is advantageous for supplementing de novo drug discovery and incorporating real-world evidence in regulatory approvals. A scoping review analyzed 250 studies, including hypothesis generation, hypothesis validation, and safety assessment. Challenges include isolated data sources, false-positive signals, bias and confounding in hypothesis validation, and the lack of regulatory guidance.
DRUG DISCOVERY TODAY
(2023)
Article
Public, Environmental & Occupational Health
Holly Foot, Carl Kirkpatrick, Grant Russell, Nancy Sturman, Amelia Cossart, Christopher Freeman
Summary: The study investigates the attitudes of GPs, patients, and practice pharmacists towards the practice pharmacist model of care in the Australian primary care setting. The results show that the model is well accepted by all stakeholders and has promising evidence for broader implementation in the healthcare setting.
RESEARCH IN SOCIAL & ADMINISTRATIVE PHARMACY
(2023)
Article
Microbiology
Guohua An, C. Buddy Creech, Nan Wu, Roger L. Nation, Kenan Gu, Demet Nalbant, Natalia Jimenez-Truque, William Fissell, Stephanie Rolsma, Pratish C. Patel, Amy Watanabe, Nicholas Fishbane, Carl M. J. Kirkpatrick, Cornelia B. Landersdorfer, Patricia Winokur
Summary: The population pharmacokinetic (PK) analysis of meropenem in 114 critically ill patients showed that the drug's clearance is affected by creatinine clearance and continuous renal replacement therapy, while volume of distribution is influenced by total bodyweight. The developed model serves as a valuable addition to the existing meropenem population PK models and is particularly useful for therapeutic drug monitoring programs with Bayesian forecasting. Monte Carlo simulations demonstrated that the dosing regimens of 2 g every 8 h with 3-h prolonged infusion (PI) and 4 g/day by continuous infusion (CI) are superior in terms of target attainment and potential toxicity when renal function information is unavailable.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Marion Hemmersbach-Miller, Stephen J. Balevic, Patricia L. Winokur, Cornelia B. Landersdorfer, Kenan Gu, Austin W. Chan, Michael Cohen-Wolkowiez, Thomas Conrad, Guohua An, Carl M. J. Kirkpatrick, Geeta K. Swamy, Emmanuel B. Walter, Kenneth E. Schmader
Summary: This study evaluated the pharmacokinetics of piperacillin/tazobactam and its changes in older adults. The estimated creatinine clearance had the most significant impact on the elimination clearance of piperacillin and tazobactam. Frailty did not have a remaining impact on their pharmacokinetics after accounting for renal function and body size.
CLINICAL PHARMACOKINETICS
(2023)
Article
Pharmacology & Pharmacy
Sam Mostafa, Thomas M. M. Polasek, Chad Bousman, Amin Rostami-Hodjegan, Leslie J. J. Sheffield, Ian Everall, Christos Pantelis, Carl M. J. Kirkpatrick
Summary: Studies that focus on individual covariates and ignore their interactions may not be adequate for model-informed precision dosing (MIPD). This study aimed to construct virtual twins (VTs) of real patients receiving clozapine with interacting covariates related to genetics and environment and to determine the impact of these interacting covariates on predicted clozapine plasma concentrations. The results showed that increasing covariate virtualization improved the accuracy and reliability of the prediction models.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Infectious Diseases
Guohua An, C. Buddy Creech, Nan Wu, Roger L. Nation, Kenan Gu, Demet Nalbant, Natalia Jimenez-Truque, William Fissell, Pratish C. Patel, Nicholas Fishbane, Amy Watanabe, Stephanie Rolsma, Carl M. J. Kirkpatrick, Cornelia B. Landersdorfer, Patricia Winokur
Summary: This study aimed to identify rational empirical dosing strategies for cefepime treatment in critically ill patients. Continuous infusion of cefepime was found to be a promising strategy with higher breakpoint coverage compared to intermittent infusions. The results of this study can serve as useful references for physicians in making dosing decisions.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Letter
Neurosciences
Thomas M. Polasek, Sam Mostafa, Carl M. J. Kirkpatrick
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
(2023)
Article
Health Policy & Services
John K. Jackson, Shane L. Scahill, Michael Mintrom, Carl M. Kirkpatrick
Summary: Since 1990, the Community Pharmacy Agreements (Agreements) between the Australian Federal government and the Pharmacy Guild of Australia (PGA) have had a significant impact on Australian community pharmacy. The Agreements primarily focus on dispensing remuneration and restrictions on the establishment of new pharmacies. Criticisms include the self-interest of pharmacy owners, lack of transparency, and impact on competition.
JOURNAL OF PHARMACEUTICAL POLICY AND PRACTICE
(2023)
Article
Pharmacology & Pharmacy
Victoria L. Oliver, Sarah Siederer, Anthony Cahn, Katarzyna Gajewska-Knapik, Rachel A. Gibson, Cleo Goodall, Carl Kirkpatrick, Jack Murray, Tri-Hung Nguyen, Ian Schneider, Pete Lambert, Michelle P. Mcintosh, Simon Parry
Summary: This study examines the role of ex vivo oxytocin metabolism and stability in late-stage pregnancy blood. The findings suggest that collecting blood into tubes containing EDTA effectively stabilizes oxytocin and inhibits oxytocinase activity. The measured concentrations of oxytocin vary between different analytical methods.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Editorial Material
Pharmacology & Pharmacy
Priya Jayachandran, Rajat Desikan, Sriram Krishnaswami, Stefanie Hennig
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Hematology
John Coutsouvelis, Carl M. Kirkpatrick, Michael Dooley, Andrew Spencer, Glen Kennedy, Maggie Chau, Gillian Huang, Richard Doocey, Tandy-Sue Copeland, Louis Do, Peter Bardy, Ian Kerridge, Theresa Cole, Chris Fraser, Travis Perera, Stephen R. Larsen, Kate Mason, Tracey A. O'Brien, Peter J. Shaw, Lochie Teague, Andrew Butler, Anne-Marie Watson, Shanti Ramachandran, Jodie Marsh, Zulekha Khan, Nada Hamad
Summary: This study aimed to describe the incidence of SOS/VOD and patterns of defibrotide use from 2016 to 2020 based on data from the Australasian Bone Marrow Transplant Recipient Registry. The incidence of SOS/VOD was 4.1% in adult centers and 11.5% in pediatric centers. Defibrotide was administered to 74.8% of adult patients and 97.3% of pediatric patients with SOS/VOD. The 100-day survival rate was 51.8% for adults and 90.4% for pediatric patients.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Surgery
Steven Ivulich, Miranda Paraskeva, Eldho Paul, Carl Kirkpatrick, Michael Dooley, Gregory Snell
Summary: Everolimus in lung transplant recipients does not increase the risk of death or accelerate the progression to chronic lung allograft dysfunction compared to calcineurin inhibitor-based immunosuppression. The emergence of chronic lung allograft dysfunction, obstructive or restrictive phenotypes, and death rates showed no significant difference between the two groups. There is a lack of long-term evidence for survival and progression to chronic lung allograft dysfunction with Everolimus-based immunosuppression.
TRANSPLANT INTERNATIONAL
(2023)
Article
Surgery
Steven Ivulich, Eldho Paul, Carl Kirkpatrick, Michael Dooley, Greg Snell
Summary: Everolimus (EVE) is an alternative immunosuppressive agent for lung transplant recipients (LTR) who cannot tolerate conventional immunosuppression. It can be used as part of a calcineurin inhibitor (CNI) minimization or elimination strategy. This study compared the safety and efficacy outcomes of EVE in LTR receiving either a CNI minimization or elimination regimen. The results showed that LTR receiving EVE as part of the CNI elimination strategy had poorer survival outcomes, while the utilization of EVE for renal preservation was associated with improved survival. The study highlighted the importance of retaining a low dose CNI in immunosuppressive regimens for superior survival outcomes.
TRANSPLANT INTERNATIONAL
(2023)