Background: Pseudomonas aeruginosa has a large armamentarium of resistance mechanisms, enabling resistance emergence against almost all antibiotics in monotherapy. Alternative treatment options are required. Aims: To evaluate regimens of meropenem (MER) and ciprofloxacin (CIP), alone and combined, against isogenic P. aeruginosa strains with different resistance mechanisms in a dynamic hollow fibre infection model (HFIM) and […]
2026
Beyond Point Estimation in the Individual Pharmacokinetics of Antimicrobials
Targeted sampling to observe individual patient pharmacokinetics is an important tool for precision dosing of antimicrobials. In conjunction with an applicable statistical model, even a small number of samples can be used to generate individual-specific estimations to guide dosing decisions. This individual-specific inference has been widely conducted by maximum-a-posteriori (MAP) estimation. This procedure is a […]
Population Pharmacokinetics of Total Intravenous Anaesthesia (TIVA) with Propofol: Limitations of Infusion/input dosing data
Introduction: Target-controlled infusion (TCI) models, such as Marsh and Schnider are commonly used for the induction and maintenance of propofol total intravenous anaesthesia (TIVA). However, substantial inter-individual variability remains in patient response, including time to loss and return of consciousness. Population pharmacokinetic (popPK) analyses require accurate dosing/input data to reliably characterise drug disposition. Problem: : […]
Mechanism-based modelling of the response of Pseudomonas aeruginosa ST235 high-risk isolates to ceftazidime/avibactam in monotherapy and combination with meropenem in a dynamic hollow fibre infection model
Background High-risk Pseudomonas aeruginosa ST235-clone causes endemics worldwide, is commonly multidrug-resistant and hypervirulent, and associated with high mortality rates. Therefore, innovative and model-informed treatment options, such as novel β-lactam combinations, are urgently needed. Aims The aim of this study was to 1) evaluate the effects of meropenem and ceftazidime/avibactam, in monotherapy and combinations, on bacterial […]
Population pharmacokinetics of daptomycin in vancomycin-resistant Enterococcus bloodstream infections
Background: Vancomycin-resistant Enterococcus faecium (VREfm) bloodstream infections (BSIs) are challenging to manage, with limited treatment options available. Daptomycin, a cyclic lipopeptide antibiotic is a key treatment agent, however optimal dosing regimens are uncertain. Daptomycin is highly protein bound (~93%) and has been reported to have significant between patient variability, including based on sex. Aims: This […]
Model-informed prediction of lipid nanoparticle-cell association across dose conditions using identifiable kinetic parameters
Objectives In vitro lipid nanoparticle (LNP) cell-association assays are widely used for formulation screening, but measured signal depends on initial dose, assay geometry, particle transport, and saturation at the cell layer. As a result, parameters estimated from a single exposure condition may not remain predictive when the dose changes. We used a model-informed workflow to […]
Mechanistic pharmacodynamic modelling of the triple artemisinin combination therapy artemether-lumefantrine (AL) plus amodiaquine (AQ)
Introduction: Antimalarial drug resistance threatens the efficacy of artemisinin combination therapies (ACTs), the first-line treatment for Plasmodium falciparum malaria. Standard ACTs combine a fast-acting artemisinin derivative with a single long-acting partner drug, whereas novel triple artemisinin combination therapies (TACTs) co-administer two long-acting partner drugs. Recent clinical trials of TACTs demonstrate favourable tolerability and high efficacy […]
A Serum–CSF Population Pharmacokinetic Model of Unbound Cefotaxime in Children
Background: Cefotaxime is commonly used empirically in bacterial meningitis, sepsis and methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia, but optimal paediatric dosing is unclear, particularly with respect to achieving adequate cerebrospinal fluid (CSF) exposure. The population pharmacokinetics (popPK) of unbound cefotaxime in serum and CSF have not been previously reported. This study aimed to (i) develop a […]
Response-Surface Pharmacodynamic Modeling to Predict Systolic Blood Pressure Reduction of a High-Dose Triple Antihypertensive Combination
Background: Contemporary hypertension treatment has shifted toward intensive blood pressure targets and earlier use of fixed-dose combination therapy. The 2024 ESC guideline further emphasizes stricter systolic blood pressure (SBP) control and preferential use of single-pill fixed-dose combinations over multiple separately administered agents. Accordingly, treatment may progress from low-dose dual-combination therapy to low-dose triple-combination therapy, followed […]
An Immunological QSP Model Incorporating Peptide-HLA Binding to Explain Variability in CD4+ T-Cell Responses to a Subunit Varicella-Zoster Vaccine
Background: T-cell response to vaccination is highly variable, making it difficult to predict vaccine efficacy from clinical trials. CD4+ T cell activation requires presentation of a pool of antigenic peptides to a diverse repertoire of T cell receptors via class II major histocompatibility complexes (MHCII) [1]. Human leukocyte antigen (HLA) molecules contain the peptide binding […]