On mass balance and the use-reuse of the rate constant matrix in pharmacokinetics

Introduction Assurance of mass balance is a critical part of pharmacometric model formulation (i.e. model creation and coding).  In many cases, for simple mamillary compartmental models this can be assessed informally.  However, in more complicated models (e.g. physiologically based models) the proof of mass balance can be more complicated.  A method to evaluate mass balance […]

A PBPK model for the clearance of nicotine and cotinine in pregnant women

Active or passive maternal smoking causes many adverse effects on fetuses. Pregnancy-related physiologically based pharmacokinetic (p-PBPK) models could help interpret nicotine¬†and its major metabolite cotinine‘s absorption, disposition, metabolism, and excretion (ADME) in pregnant women. This talk presents a p-PBPK model and its simulations for nicotine and cotinine. The maternal-placental-fetal compartments of the p-PBPK model contain […]

Finding the unknown parameters of a viral kinetics model of Covid-19 with immune response

The global pandemic caused by the outbreak of Covid-19 (SARS-CoV-2) remains to be an unsolved issue worldwide and has caused major uncertainties in our lives. This work models the viral kinetics of Covid-19, where the replication and elimination of the virus can be modelled using a system of ordinary differential equations (ODE). The unknown parameters […]

Time Course of Procalcitonin – Imputation of Missing Clock Times

Background: Concentrations of endogenous procalcitonin (PCT) increase within hours of infection, and after events such as birth and surgery [1]. Determining the natural history of procalcitonin may help identify abnormal increases indicative of infection. However, in the dataset only the date of observations are recorded without the clock times [2]. If clock times are unavailable, […]

Open-Source Software for Vancomycin Therapeutic Drug Management in a Vietnamese hospital

Introductions: This study aims to assess and identify a suitable population pharmacokinetic (POP PK) model for vancomycin using concentration data from Vietnamese patients. The proper POP PK model was then utilized to construct a Bayesian tool to improve the quality of TDM service in Vietnam. Methods: Reviewing literature in Pubmed and the sites of available […]

Last-mile delivery: a reference plot to help non-pharmacometricians interpret population pharmacokinetics results

BACKGROUND: Although pharmacometricians have put great efforts into transitioning the modeling results via simulations to facilitate the appropriate dosing, there is still a knowledge gap for frontline practitioners to understand the raw results from population pharmacokinetics (PopPK) analysis and subsequently make a meaningful interpretation to guide clinical practice. A practical tool is warranted to fill […]

In silico modelling for transplacental transfer of morphine in an ex vivo human cotyledon perfusion system

Transplacental properties of drugs are important for the well-being of fetuses. However, in vivo data on the transplacental effects of most drugs are rare due to ethical issues and technical challenges. Hence, ex vivo placenta cotyledon perfusion experiments have been used to investigate the transplacental properties since the 1960s. Recently there have been some efforts […]

A parametric repeated time-to-event modelling of recurrent ischemic stroke after index stroke among patients with diabetes mellitus

Objectives: Diabetes (DM) is associated with an increased risk of recurrent ischemic stroke (IS). A temporal description of an increased or decreased risk of recurrent IS among diabetic patients is not fully established. This study aimed to investigate the repeated time-to-event of recurrent IS after the index IS among patients with diabetes using a parametric […]

Patient-reported outcomes predict survival and adverse events following anticancer medicines initiation

Background The prognostic value of patient-reported outcomes (PROs) has been minimally explored in advanced breast cancer, and their comparative prognostic performance against Eastern Cooperative Oncology Group performance status (ECOG PS) is largely unknown. Methods This study pooled individual participant data from clinical trials CLEOPATRA, EMILIA, and MARIANNE. Pre-treatment PRO associations with overall survival (OS), progression-free […]

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 […]