Pharmacokinetic-Pharmacodynamic informed labelling for Machine Learning classification tasks: predicting severe neutropenia using Real World Data

Introduction: Real-world data (RWD) from electronic health records provide a rich source of information about patient trajectories and outcomes. Machine learning (ML) models can make use of these large datasets to identify significant features and patterns associated with drug effect or safety. However using clinical RWD in ML modelling can be challenging due to sparse, […]

Population pharmacokinetics of milrinone in premature neonates to adolescents

Introduction: Milrinone is an inotrope and vasodilator used for prophylaxis or treatment of low cardiac output syndrome after weaning from cardiopulmonary bypass (CPB). It is renally eliminated and has an acceptable range of 100 – 300 μg/L, but weight-based dosing alone is associated with poor target attainment [1].Aims: To develop a population PK model for […]

Cefazolin pharmacokinetics and extent of device binding during cardiopulmonary bypass

Introduction: Cefazolin is administered routinely for antibiotic prophylaxis during cardiac surgery. However there is uncertainty in determining the correct dose due to the impact of critical illness and the cardiopulmonary bypass (CPB) machine on drug pharmacokinetics (PK). Aims: To quantify cefazolin adsorption to the CPB machine device and incorporate this into a population PK model […]

An ex vivo study measuring antibiotic adsorption to cardiopulmonary bypass circuitry

Background: Cephazolin and vancomycin are commonly used for antibiotic prophylaxis during surgery supported by cardiopulmonary bypass (CPB). Antibiotic pharmacokinetics (PK) can be altered by CPB through haemodilution, haemofiltration, hypothermia and drug adsorption to the circuitry (1). Adsorption can contribute to decreased antibiotic concentrations with consequent reduced prophylactic effectiveness (2). Highly protein bound drugs like cephazolin […]