Background Linezolid belongs to oxazolidinone class of antibiotics and is primarily used for the treatment of sever infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus (VRE). It inhibits bacterial protein synthesis by blocking the formation of initiation complex in ribosomes. Linezolid is eliminated through both renal and hepatic routes. It is classified […]
Abstracts
Evaluation of a pharmacokinetic-pharmacodynamic model for predicting parasitological outcomes in Phase 2 studies of new antimalarial drugs
Introduction: The rise of multidrug resistant malaria demands the urgent development of novel antimalarial compounds. For a drug to achieve registration and availability in the market, new treatments must undergo a series of rigorous evaluations, from preclinical studies in human volunteers experimentally infected with malaria, through to Phase 3 clinical trials in malaria patients. Pharmacokinetic-pharmacodynamic […]
Pharmacometrics Insights into Major Bleeding Risk in Rivaroxaban-treated Atrial Fibrillation Patients
Introduction: Pharmacometrics time-to-event (TTE) modelling complements therapeutic drug monitoring (TDM) in assessing drug efficacy and safety. In atrial fibrillation (AF) patients on rivaroxaban, heart failure (HF) is an independent predictor of bleeding. Given rivaroxaban’s high protein binding and hepatic metabolism, organ congestion in HF may influence drug disposition and anticoagulation outcomes. Objectives: This study aimed […]
Double-Blinded External Evaluation of Predictive Performance: pyDarwin vs. Human Expert in a Paediatric Tobramycin Population PK Model Development
Introduction: Paediatric population pharmacokinetic (PopPK) model development is complex due to physiological changes occurring throughout growth and maturation. pyDarwin, an open-source Python package, integrates machine learning with NONMEM for model selection, but its capability in handling complex paediatrics PopPK model selection remains unvalidated. A double-blinded external comparison of the pyDarwin-selected and manually-developed models is necessary […]
Evidence-based medication practice of rifapentine in Chinese adults with HIV and latent tuberculosis infection
Introductions: Tuberculosis is the most common comorbidity among people living with HIV (PLWH) and remains a leading cause of HIV-related mortality worldwide. Early preventive treatment for latent tuberculosis infection (LTBI) is essential to prevent disease progression and reduce transmission. Recently, the one-month daily combination of rifapentine and isoniazid (1HP) regimen has demonstrated high efficacy and […]
Mechanism-based modelling of the response of Enterobacterales with different resistance mechanisms to a newly approved β-lactam/β-lactamase inhibitor combination
Background Carbapenem-resistant Enterobacterales, such as Klebsiella pneumoniae and Escherichia coli, are considered critical priority pathogens by the World Health Organization. These pathogens produce an extensive range of β-lactamases, including New Delhi metallo-β-lactamases (NDM) which render most β-lactams inactive. The newly approved β-lactam/β-lactamase inhibitor combination aztreonam/avibactam shows promise in treating these pathogens; however, penicillin-binding protein (PBP) […]
The Next Dose Transfer Story
Introduction: NextDose is a web based dosing tool (www.nextdose.org) that was developed at the University of Auckland (UoA) in 2012 (Holford et al., 2012). The tool provides a target concentration approach to dosing, currently for 17 medicines. The most frequently used are vancomycin, busulfan, gentamicin and warfarin. The tool is provided at no cost to the […]
Leveraging Machine Learning to Decode Polymeric Long-Acting Injectables and Predict Their Performance
Introduction Polymeric long-acting injectables (LAIs) enhance chronic disease treatment by prolonging therapeutic duration, reducing dosing frequency, and improving patient compliance [1, 2]. Evaluating drug release kinetics—particularly burst release and sustained release—is critical for LAI quality assessment, yet traditional methods face limitations, necessitating predictive modeling [2]. Key challenges include functional data prediction and datasets constraints, which […]
Multi-objective Optimization for Population Pharmacokinetic Model Selection in pyDarwin
Introduction:The selection of the “best” model typically involves both objective (numerical) and subjective criteria, such as interpretation of plots and consideration of biological plausibility. Multi Objective Optimization (MOO) allows for the simultaneous optimization of multiple criteria. This approach generates a Pareto front, representing a set of non-dominated models where no single solution can be improved […]
ADPO: Automatic-differentiation-assisted parametric optimization algorithm
Objectives: Compare two alternative approaches to parameter estimation using the first-order conditional estimation with interaction (FOCE-I) method in mixed-effect non-linear regression for efficiency and robustness. Methods: Typically, in the FOCE-I, finite difference (FD) is used to approximate the gradient. FD is a numerical approximation to the gradient, accomplished by calculating the objective function value at […]