Background: Syphilis remains a global public health concern, particularly in pregnancy due to the risk of congenital syphilis. The World Health Organization recommends benzathine penicillin G (BPG) as the standard treatment in pregnant women, whilst the optimal dosing strategy has not been established, particularly in relation to the impact of gestational age. This study sought […]
2026
Joint serum-cerebrospinal fluid population pharmacokinetic modelling and dose optimisation of aciclovir in children aged 0-<18 years
Introduction. Aciclovir is an antiviral widely used to treat herpes simplex virus (HSV) infections, including neonatal HSV encephalitis, where adequate serum and cerebrospinal fluid (CSF) exposure is needed. However, a paediatric population pharmacokinetic (PopPK) model characterising CSF penetration remains absent. Aims. To develop a joint serum–CSF PopPK model in children aged 0–18 years to optimise […]
POPULATION PHARMACOKINETIC-PHARMACODYNAMIC MODELLING OF FOLLICLE-STIMULATING HORMONE AND INHIBIN-B TO PREDICT OVARIAN RESPONSE TO FOLLITROPIN ALFA IN IN VITRO FERTILISATION PATIENTS
Introduction/Objectives: Controlled ovarian hyperstimulation (COH) in women undergoing in vitro fertilisation (IVF) involves daily administration of recombinant follicle-stimulating hormone (FSH; follitropin alfa) to stimulate follicular maturation. As follicles grow, they initially secrete inhibin-B [1], making inhibin‑B a sensitive biomarker of early ovarian response. Substantial inter‑individual variability exists in FSH pharmacokinetics, meaning optimising the number of […]
Deprescribing allopurinol in a typical gout patient receiving haemodialysis: A PKPD simulation
Introduction. Allopurinol, a urate-lowering therapy used to manage gout, is commonly prescribed in patients receiving haemodialysis (HD). Urate is effectively removed by HD raising the question of whether allopurinol is needed to achieve the serum urate (SU) target of < 0.36 mmol/L. Aims. To simulate SU concentration changes for a typical gout patient with CKD […]
Population Pharmacokinetics/Pharmacodynamics (PK/PD) of Rivaroxaban in Atrial Fibrillation: Impact of Ventricular Function and Hepatic Markers
BACKGROUND: Rivaroxaban PK is highly sensitive to hemodynamic variations due to dual renal and hepatic elimination. While heart failure (HF) alters drug disposition, the impact of quantitative ventricular metrics like left ventricular ejection fraction (LVEF) on PK rivaroxaban remains poorly characterized. This study aims to develop and externally validate a population PK/PD model of rivaroxaban […]
Bridging Literature and Real-World Evidence: External Evaluation of Daptomycin Population Pharmacokinetic Models to Advance Precision Dosing in Elderly Patients
Introduction: Daptomycin is a key antibiotic for multidrug-resistant Gram-positive infections, but its substantial inter-individual pharmacokinetic variability and exposure-related efficacy and toxicity make optimal dosing challenging, particularly in elderly patients. Age-related changes in renal function may further alter daptomycin exposure, increasing the risk of underexposure or toxicity. Population pharmacokinetic (PopPK) models provide the foundation for model-informed […]
A Mathematical Framework for Quantifying CB1 Receptor Internalization in the Presence of Allosteric Modulators
Introduction: Type 1 Cannabinoid Receptor (CB1) is the most abundant receptor in human brain and regulates multiple physiological activities via triggering downstream signalling network. CB1 internalisation is part of the signalling network, causing desensitization and this is a highly dynamic process. Orthosteric ligand (OL) could bind to endocannabinoids’ binding site and allosteric modulator (AM) could bind […]
Pharmacokinetics of benzathine penicillin G in pregnant women with syphilis
Background: Syphilis in pregnancy remains a global public health concern, due to the risk of adverse birth outcomes. The World Health Organization recommends benzathine penicillin G (BPG) in pregnant women, although the optimal dosing strategy has not been clearly established, particularly in relation to the impact of gestational age. This study sought to characterize the […]
Clinical trial simulation to explore AUC-guided vancomycin dosing
Background: Vancomycin dosing is commonly adjusted using therapeutic drug monitoring (TDM), traditionally guided by trough concentrations. An Auckland before-after cohort study evaluated a local change from empirical trough-guided TDM to NextDose-informed Bayesian 24-hour area under the concentration-time curve (AUC24)-guided target concentration intervention (TCI). In routine care, dosing performance is shaped by pharmacokinetics and ward execution, […]
Next-generation mechanism-based mathematical model describing the response of twelve Pseudomonas aeruginosa strains with diverse resistance mechanisms to aztreonam, ciprofloxacin, and their synergistic combination therapy.
Background. Developing next-generation mechanism-based mathematical models (ngMBMs) that incorporate characteristics of bacterial strains as predictors of bacterial response to antibiotic treatment is essential to support model-informed precision dosing of antibiotics. This study aimed to develop a ngMBM that describes the time-courses of bacterial responses of 12 Pseudomonas aeruginosa (PA) strains with various resistance mechanisms treated […]