Favipiravir pharmacokinetics in infants and young children with chronic RNA viral infections

Background  Favipiravir selectively inhibits RNA polymerase responsible for single-stranded viral replication. It is licensed for treating influenza and repurposed to treat other diseases such as Ebola1 and COVID-192. It is metabolised by hepatic aldehyde oxidase (AO) and is an AO inhibitor with complex pharmacokinetics. AO expression is shown to rapidly increase in first two years […]

A consistent nomenclature for describing pharmacokinetics and dialyser performance

Introduction: Since renal dialysis machines were introduced into clinical practice in the 1950s, dialysis has immensely evolved to become the core treatment for patients with end stage renal disease. However, quantifying dialysis performance and its effect on medication clearance is still challenging. The Michaels equations, often used  to calculate blood dialysance, were derived for 3 different […]

Pharmacodynamic modelling approaches in the setting of suboptimal drug adherence

Introduction. Suboptimal adherence may bias pharmacokinetic (PK) parameter estimates.1 Rather than conditioning the PD response on the model predicted PK response, an alternative approach is to fit a kinetic-pharmacodynamic (KPD) model in which the PK data are excluded from the analysis. KPD models may be an advantage in such scenarios because the KPD analysis allows […]

A Complete Bayesian Workflow in Pumas

In this work, we present the Bayesian workflow in the Pumas software for pharmacometrics (PMx) that’s: 1) demonstrably correct, 2) computationally efficient, and 3) user-friendly. Correctness-wise, Stan and its ecosystem of R packages arguably form the gold standard for Bayesian analysis of models that have many continuous parameters, which is the class of models commonly […]

Time Course of Procalcitonin Concentration Following Birth and Surgery

Introduction: Procalcitonin plasma concentration (PCT) has been suggested as a biomarker for acute infection (usually bacterial). Concentrations increase rapidly within 4-6 hours of infection [1]. However PCT also increases following events such as birth and surgery without any known infection [2, 3]. It is important to understand the time course of PCT following these events […]

The impact of birth on propofol clearance maturation

Introduction: Propofol is used for the induction and maintenance of anaesthesia in neonates, infants and children. Clearance is the pharmacokinetic parameter that determines maintenance infusion rates and clearance matures over the first years of life. Postmenstrual age (PMA) is typically used to quantify clearance maturation as it accounts for maturation that begins in utero. Maturation […]

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 […]

Mixed-effect meta-analysis of published NCA data for Cannabidiol

Introduction: Cannabidiol (CBD) is non-psychotomimetic phytocannabinoid obtained from Cannabis Sativa (marijuana). It has received significant interest in the medical field due to its anti-inflammatory, anti-oxidative and anti-necrotic effects. Moreover, CBD has promising safety and tolerability profile making it a potential treatment for several diseases including Parkinson’s disease, Alzheimer’s disease, and Epilepsy among others.  Nevertheless, the […]

New Insights into the Pharmacokinetics of Gentamicin, Amikacin and Vancomycin – from Neonates to Adults

A joint model of the pharmacokinetics of gentamicin, amikacin and vancomycin with a wide dispersion of age, size and renal function was developed by pooling data from around the world. Data was contributed by Karel Allegaert (Belgium), Amilcar Falcao (Portugal), Nicolas Simon (France), Lin Lo (Malaysia), Alison Thomson (Scotland), Catherine Sherwin (New Zealand and USA), […]