Background: Common approaches for handling of concentration measurements reported as below the limit of quantification (BLQ), such as discharging the information or substitution with the limit of quantification (LOQ) divided by two, have been shown to introduce bias to parameter estimates [1,2,4-6]. In 2001, Stuart Beal published an overview of ways to fit a PK model […]
Abstracts
Mechanistic Modeling of Magnetically Marked Extended Release Formulation of Felodipine
Background: Magnetic Marker Monitoring is a novel technique for visualising the transit of a solid oral dosage form through the GI tract. For dosage forms with erosion controlled drug release, the technique can also be used for obtaining an in-vivo drug release profile [3]. Aim: To assess information gained by a mixed effect modeling approach to data […]
Pharmacokinetics of L-arginine after intravenous infusion in adults with moderately severe malaria
Background: Plasma L-arginine is a naturally occurring amino acid that has been found to be reduced in patients with malaria to concentrations below the equilibrium constant (Km) of the cationic amino acid transporter (CAT) needed for intracellular transport and may limit cellular nitric oxide (NO) production. Aim: To develop a pharmacokinetic model for L-arginine in adults with […]
Normalized prediction distribution errors for the evaluation of nonlinear mixed-models
Context: Although population pharmacokinetic and/or pharmacodynamic model evaluation is highly recommended by regulatory authorities, there is no consensus today on the appropriate approach to assess a population model. We have also shown in a recent literature survey [1] that model evaluation was not appropriately performed in most published population pharmacokinetic-pharmacodynamic analyses. Among the different approaches proposed […]
Lean Body Weight versus Total Body Weight as a Covariate for Clearance
Background: When conducting population pharmacokinetic (PK) analyses, total body weight (WT) is often chosen as a covariate to explain between subject variability in clearance (CL). Given that 99% of the body’s clearance takes place within lean tissues, it has been suggested that WT is unlikely to be suitable for obese subjects and lean body weight (LBW) […]
Preclinical Population PK/PD of TGF beta RI Kinase inhibitor for Cancer
Objectives: The primary objective of PK/PD modeling in preparation for the First Human Dose study was to estimate a pharmacologically effective dose range in humans based on preclinical data Methods: Data from tumor growth kinetics Xenograft model in mice and from in vivo target inhibition (IVTI) in rats and in mice were incorporated in our PK/PD […]
Population pharmacokinetic analysis of morphine in opioid dependent and control subjects
Background: Pilot data (n=4 per group) suggests methadone maintenance subjects (MMS) may have increased plasma morphine concentrations compared with controls after the same iv dose (1). Morphine is primarily cleared by hepatic glucuronidation, which is inhibited by methadone in vitro (2). There has been no previous reported investigation of morphine clearance in the presence of buprenorphine. Targeting of specific […]
Development of a sufficient design for parameter estimation of fluconazole population pharmacokinetics in HIV patients
Introduction: Fluconazole (FCZ) is an antifungal drug commonly used in HIV patients. A clinician suspected low concentrations of FCZ in HIV patients, which could be due to saturable input (low bioavailability) or nonlinear disposition of the drug. In contrast, the literature suggests that FCZ concentrations are increased in HIV patients. A study found in the literature […]
Tobramycin in paediatric CF patients – TCI or
Aim: The aim of this study was to i) develop a population pharmacokinetic model for tobramycin in paediatric cystic fibrosis (CF) patients ii) evaluate the influence of covariates, in particular serum creatinine, and iii) test whether tobramycin in CF patients is a candidate for the use in target concentrations intervention (TCI). Methods: Retrospective demographic, dosing and concentration […]
Comparison of different diagnostic criterion to evaluate nonlinear mixed-effects models
Background: The use of conditional weighted residual (CWRES) and post-hoc ETA (ηph) distribution properties, instead of weighted residual (WRES) distribution properties, as model diagnostic tools when using the first-order conditional (FOCE) algorithm in NONMEM, may give a more accurate picture of if and when a model is miss-specified. Aim: A simulation study was performed to compare these […]