Can PBPK Models Predict Post-Mortem Redistribution?

Background:  Post-mortem redistribution (PMR) refers to changes in drug concentrations that can occur after death due to various processes such as passive diffusion from solid organs.1  Drug concentrations can also differ significantly depending on the site from which the specimen was taken.2  This can cause confusion for those trying to establish a cause of death as ‘toxic’ […]

Population pharmacokinetics of oxypurinol in patients with gout receiving allopurinol

Background: Allopurinol, a pro-drug of oxypurinol, is the most common medicine used for prophylactic management of gout. The active metabolite of allopurinol, oxypurinol, is responsible for the urate lowering effect of allopurinol and is primarily renally excreted. Treatment response to allopurinol is variable in people with gout supporting the need for more information about factors which […]

Optimal designs for population pharmacokinetic studies of a drug with large assay variability for patients with restrictive sampling schedules

Objective: This work aimed to determine an optimal design for patients with restrictive sampling schedules who received a drug* that displays huge assay variability, is rapidly absorbed and has a very short elimination half-life. Methods: Rich data from 20 patients were modelled in R (using nlme) to determine the structural pharmacokinetic (PK) model, PK parameters, inter-patient and […]

Pharmacokinetics of Chloroquine in Pregnant and Non-pregnant Women in Papua New Guinea

Background: Pregnant women are one of the groups for which malaria presents a particular concern, not only for the mother but also the fetus. Treatment of symptomatic infections and the use of intermittent preventive treatment in pregnancy (IPTp) may help reduce malaria associated maternal and infant morbidity and mortality. Despite the widespread use of conventional antimalarials […]

The population pharmacokinetics of propofol: a meta-analysis of studies available from the OpenTCI Initiative

Aim: The aim of this study was to develop a population PK model for propofol in adults that could be used to determine optimal sampling times for a prospective pharmacokinetic study. Methods: Data from 15 pharmacokinetic studies of propofol in adults were obtained from the OpenTCI Initiative [1]. A total of 7711 concentrations from 405 […]

Understanding intranasal fentanyl for acute pain treatment in children: randomized controlled trials or population pharmacodynamic studies?

Introduction: The use of intranasal fentanyl for pain relief in children’s emergency departments is gaining popularity following the publication of a randomised controlled trial showing intranasal fentanyl to be as effective as intravenous morphine while being easier to administer1. Unfortunately, intranasal fentanyl is being used with younger children, higher doses, and with a different formulation to […]

Does the use of Lean Body Weight (LBW) in a modified Cockcroft-Gault (C-G) equation provide a better prediction of gentamicin clearance?

Background: The Cockcroft and Gault (C-G) method of calculating creatinine clearance (CLcr) does not appear to perform well at low concentrations of serum creatinine and the extremes of body sizes. Aim:  To evaluate the performance of a modified C-G equation to predict gentamicin clearance. Methods: Demographics and gentamicin pharmacokinetic parameters were collected from 999 subjects as part of […]

The Effect of Study Design on Pharmacokinetics in Patients with Impaired Renal Function

Backgroud: To ensure the effect of renal function on drug exposure is precisely quantified, FDA guidance1recommends that studies recruit approximately equal subject numbers with normal renal function and mild, moderate and severe renal impairment. However, in population PK analyses it is common to pool data from various studies, resulting in an over-representation of subjects with normal […]

A nonlinear mixed effects model to characterise lamivudine absorption and distribution

Background: Lamivudine (3TC), a potent selective inhibitor of HIV reverse transcriptase, is used in combination antiretroviral therapy (ART). 3TC pharmacokinetics is characterised by highly variable absorption and is rapidly distributed to a slow equilibrating peripheral compartment. Although not considered a candidate for routine therapeutic drug monitoring, 3TC pharmacokinetics is unaltered by concomitant anti-tuberculosis treatment, a […]