Archive | Abstracts

Extrapolation of acetaminophen PK models from adults to paediatricians

Extrapolation of PK models from adults to paediatricians requires re-qualification of physiological and pharmacokinetic parameters. Specifically, maturation of metabolism pathways, urinary clearance and rapid weight changes in paediatricians affect PK profiles. In this presentation we describe a case study of extrapolating a clinical acetaminophen (APAP) PK model from adults to neonates (<28 days) and infants […]

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How many NMLE articles are published in higher Impact Factor clinical journals?

Background: Pharmacometrics aims to understand the drug-patient interaction, connects various fields such as physiology, pharmacology, pharmacotherapy, clinical pharmacy, mathematical modelling, statistics, systems biology, pharmacokinetics/-dynamics in a coherent framework to improve drug development and patient therapy outcomes. The aim of this review was to identify publications that have applied the nonlinear mixed effects (NLME) modelling approach […]

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Pharmacodynamic effect of evogliptin on bone metabolism in healthy menopausal women

Background: DPP-IV has a role in degradation of glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), and gastric inhibitory polypeptide (GIP) which had been reported to reduce bone resorption. We investigated the pharmacodynamic effect of evogliptin, a DPP-IV inhibitor, on human bone metabolism in human using serum carboxy-terminal collagen crosslinks (CTX) as a biomarker of bone resorption. Method: […]

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Combining PK and PD data; a 20 year perspective

Twenty years ago there were already many publications about population PK/PD analyses, but no research had been done on the best way to combine PK and PD data. A fundamental assumption of PK/PD analyses was that the PK response drives the PD response. Analysing PK and PD simultaneously was considered to be the gold standard, […]

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Implementation of an approximate input forcing function for modelling single tissues in the Open Pharmacology Suite

Objectives: The PK-Sim®software is used for the development of whole-body physiologically-based pharmacokinetic (PBPK) models. During model development parameters for drug disposition must be provided, often sourced from in vivo/in vitro experiments. If these parameters are influential, misspecification in a single organ can impact the entire PBPK model. Through development of single-tissue models, initial estimates for influential parameters […]

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From the First to the NextDose: My journey through 20 years of PAGANZ

Our overarching aim has been to bring better dosing methods to the ward, meaning we aim not only to make pharmacometric model-based calculations useable by clinicians, but to actually get them to use it. We want doses to be determined by the best possible method, meaning real patients receiving doses that were determined (at least […]

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The Influence of Genotype on Warfarin Dose Predictions

Background & Aims: Warfarin is the most commonly prescribed oral anticoagulant worldwide, however, a narrow therapeutic range poses a barrier to safe and effective therapy. Common methods to predict warfarin dose requirements are biased at the extremes. When evaluated by simulation, Bayesian dose forecasting using a theory-based warfarin PKPD model achieves unbiased and precise dose predictions […]

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A Population Pharmacodynamic Study of Apnea of Prematurity and the Effect of Caffeine Citrate in Chinese Premature Neonates

Objective: Apnea of prematurity (AOP) is defined as an attack of apnea for at least 20 seconds, with bradycardia and cyanosis. It is a common phenomenon in the neonatal intensive care unit (NICU). Caffeine is used to suppress or to prevent AOP attacks. Based on a population pharmacokinetic (PK) model for caffeine the effect of caffeine […]

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Evaluation of study designs to test the intact nephron hypothesis

Introduction: Renal dose adjustment generally assumes a linear relationship between renal drug clearance (CLR) and glomerular filtration rate (GFR). The theory underpinning this practice is the Intact Nephron Hypothesis (INH) [1]. A recent review by our group suggested that the INH may not be a suitable general model for renal drug clearance, particularly for drugs that […]

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Analyzing endpoints with many ordered categories: theory and applications

Background: Longitudinal exposure-response (E-R) modeling of clinical endpoints is important in drug development to identify optimal dose regimens. Clinical endpoints are often ordinal composite scores. Typically, endpoints with few (e.g., <6) categories are analyzed as categorical, and endpoints with many (≥10) categories are analyzed as continuous. Endpoints with many categories often show skewed distributions that […]

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