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 […]
Archive | Abstracts
How many NMLE articles are published in higher Impact Factor clinical journals?
January 12, 2019
Authors Stefanie Hennig (1), Charlotte Kloft (2)
Affiliations 1. University of Queensland, Brisbane, Australia; Alexander von Humboldt Foundation, Germany 2. Insitute fuer Pharmazie, Freie Universitaet Berlin, Berlin, Germany
Presentation type Oral
Presenters Stefanie Hennig
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 […]
Pharmacodynamic effect of evogliptin on bone metabolism in healthy menopausal women
January 10, 2019
Authors Namyi Gu (1), Moo-Yong Rhee (2)
Affiliations 1. Department of Clinical Pharmacology and Therapeutics, Dongguk University College of Medicine and Ilsan Hospital, Goyang, 2. Department of Internal Medicine, Dongguk University College of Medicine and Ilsan Hospital, Goyang
Presentation type Poster
Presenters Namyi Gu
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: […]
Combining PK and PD data; a 20 year perspective
January 10, 2019
Authors Janet R Wade
Affiliations Occams
Presentation type Oral
Presenters Janet R Wade
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, […]
Implementation of an approximate input forcing function for modelling single tissues in the Open Pharmacology Suite
January 10, 2019
Authors Jim H. Hughes (1), Richard N. Upton (1), Stephanie E. Reuter (2), Mitch A. Phelps (3, 4), David J.R. Foster (1)
Affiliations 1. Australian Centre for Pharmacometrics, School of Pharmacy and Medical Sciences, University of South Australia, 2. School of Pharmacy and Medical Sciences, University of South Australia, 3. Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 4. Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH
Presentation type Oral
Presenters Jim H. Hughes
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 […]
From the First to the NextDose: My journey through 20 years of PAGANZ
January 7, 2019
Authors Sam Holford, Nick Holford
Affiliations University of Auckland
Presentation type Oral
Presenters Sam Holford
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 […]
The Influence of Genotype on Warfarin Dose Predictions
January 7, 2019
Authors Guangda Ma (1), Nick Holford (1), Jacqui Hannam (1), Jeff Harrison (1)
Affiliations 1. The University of Auckland
Presentation type Oral
Presenters Guangda Ma
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 […]
A Population Pharmacodynamic Study of Apnea of Prematurity and the Effect of Caffeine Citrate in Chinese Premature Neonates
January 6, 2019
Authors Nick HOLFORD (2)，Xiaoyan YANG (1)，(2)，Zhimei JIANG (3)，Hongxin SHEN (3)，Jing SHI (1)，Xianxiao SHU (1)，Yi HUANG (1)，Jing ZHAO (1)，Jun TANG (1)，Dezhi MU (1)
Affiliations 1. Department of Pediatrics, West China Second University Hospital, Sichuan University Chengdu 610041, China; 2. Dept Pharmacology & Clinical Pharmacology, University of Auckland, Auckland 1010, New Zealand; 3. Department of Pharmacology, West China Second University Hospital, Sichuan University Chengdu 610041, China
Presentation type Oral
Presenters Nick Holford
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 […]
Evaluation of study designs to test the intact nephron hypothesis
January 6, 2019
Authors Sudeep Pradhan, Daniel F.B. Wright, Stephen B. Duffull
Affiliations University of Otago
Presentation type Oral
Presenters Sudeep Pradhan
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 […]
Analyzing endpoints with many ordered categories: theory and applications
January 6, 2019
Authors Chuanpu Hu (1), Honghui Zhou (1), Amarnath Sharma (1)
Affiliations 1. Janssen Research & Development
Presentation type Oral
Presenters Chuanpu Hu
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 […]