Abstracts - PAGE Meeting (Population Approach Group Europe)

R.R. Press(1), B.A. Ploeger(2,3), J. den Hartigh(1), R.J.H.M. van der Straaten(1), J. van Pelt(1), M.Danhof(2,3), J.H. de Fijter(1), H.J. Guchelaar(1).

Dose prediction of tacrolimus in de novo kidney transplant patients with population pharmacokinetic modelling.

Balaji Agoram, Steven Martin, Piet van der Graaf.

Application of mechanism-based population PKPD modelling in the rational selection of clinical candidates: an anti-IgE antibody example.

K. Kuester(1,3), A. Kovar(2), B. Brockhaus(2), C. Kloft(1,3)

Matuzumab – A Population Pharmacokinetic Model and its Evaluation

Christian Laveille(1), Eric Snoeck(1), Brigitte Lacroix(2), Maria Laura Sargentini-Maier(2), Armel Stockis(2)

Dose-response population modeling of the new antiepileptic drug brivaracetam in add-on treatment of partial onset seizures.

Etienne Pigeolet(1), PhilippeJacqmin(2), Maria Laura Sargentini-Maier(1), G. Parker(1) and Armel Stockis(1).

Population pharmacokinetics of certolizumab pegol

Clare Gaynor (1), Adrian Dunne (1) and John Davis (2)

An assessment of prediction accuracy of two IVIVC modelling methodologies.

RJ Bauer (1), S Guzy (1), CM Ng (2)

A Comparison of Estimation Methods in Nonlinear Mixed-effect Model for Population Pharmacokinetic-pharmacodynamic Analysis

R. Lledó-García (1), M. Merino Sanjuán (1), L. Prats (1), A. Nácher (1), V.G. Casabó (1)

Population Pharmacokinetics of Saquinavir in rats after IV and IP administration. An approach to Saquinavir/Ritonavir Pharmacokinetic interaction.

Robert H. Leary

An evolutonary nonparametric NLME algorithm

S. Albers (1), B. Meibohm (2), J. Barrett (3), TS. Mir (4), S. Laer (1)

Population Pharmacokinetics and Dose Simulation of Carvedilol in Pediatric Patients with Congestive Heart Failure

Neil Benson1, Nelleke Snelder2, Bart Ploeger2 , Carolyn Napier1, Harriet Sale1 and Piet van der Graaf1

Utility of a mixed effects approach to defining target binding rate constants.

Emma Boström, Margareta Hammarlund-Udenaes and Ulrika SH Simonsson

Blood-brain barrier transport helps explain discrepancies in in vivo potency between oxycodone and morphine

Ihab G. Girgis, Tom Schaible, Partha Nandy, Filip De Ridder, Jeffrey Mathers, and Surya Mohanty

Parallel Bayesian Methodology for Population Analysis

Leonid Gibiansky

Precision of Parameter Estimates: Covariance Step ($COV) versus Bootstrap Procedure

D. Hirt, F. Mentré, A. Tran, E. Rey, S. Auleley, X. Duval, D. Salmon, J.M. Tréluyer, and the COPHAR2- ANRS study group.

Effect of CYP2C19 polymorphism on nelfinavir to M8 biotransformation in HIV patients.

Matthews, I and Aarons, L

Sensitivity analysis of a mixture model to determine genotype/phenotype

Dittberner, S. (1), V. Duval (2), A. Staab (2), I. Troconiz (3), U. Graefe-Mody (2), U. Jaehde (1)

Determination of the absolute bioavailability of BI 1356, a substance with non-linear pharmacokinetics, using a population pharmacokinetic modelling approach

Soy D1, Clopés A2, Farré R3, Mangues MA3

Population Pharmacokinetic Modeling Of Busulfan In Patients Undergoing Autologous Stem Cell Transplantation (ASCT) For Multiple Myeloma

X Delavenne (1), T Basset (2), P Girard (3) , H Decousus (1,4), P Mismetti (1,4), S Laporte (1)

The use of an indirect response model to assess interaction between drugs: acenocoumarol and amoxicillin + clavulanic acid

M.A. Fabre (2), E. Fuseau (2), A. Vermeulen (1), A. Thyssen (1).

Population pharmacokinetic analysis in children, adolescents and adults with schizophrenia or bipolar disorder

Didier Concordet, Djalil Chafaï

How to estimate population variance matrices with a Prescribed Pattern of Zeros?

Emmanuelle Comets (1), Karl Brendel (2) and France Mentré (1,3)

Normalised prediction distribution errors in R: the npde library

Yumi Fukushima (1), Jean-Eric Charoin (1), Michael Brewster (2), E. Niclas Jonsson (1)

Population Pharmacokinetic Analysis of Trastuzumab (Herceptin®) based on Data from Three Different Dosing Regimens.

Vincent Buchheit, Marie-Odile Lemarechal, Caterina Ferioli, Aurelie Gautier, Gregory Pinault, Kathy Chen*, Goonaseelan (Colin) Pillai, Jean-Louis Steimer

A dedicated SAS Programming Group working in a pharmaceutical Modeling & Simulation organization – Current role, experience and prospects

K.H. Liesenfeld, J. Stangier, H.G. Schaefer, A. Staab

How can routinely collected comedication information from phase II/III trials be used for screening of potential effects on model parameters? A case study with the oral direct thrombin inhibitor Dabigatran etexilate

Kevin M. Krudys, Oscar Della-Pasqua

Can Bayes Prevent QTC-interval prolongation? A challenge beyond random effects.

P. Johnson (1), H. Dai (2), S. Neelakantan (2), T. Tensfeldt (2)

Optimal dose & sample-size selection for dose-response studies

M. Vernaz-Gris (1), E. Fuseau (1), L. Del Frari (2), V. Brunner (2), P. Hermann (2)

Pooled PK analysis of a new CNS drug, in healthy subjects.

Aris Dokoumetzidis

An algorithm for proper lumping of systems of ODEs

Wojciech Krzyzanski (1) and Juan Jose Perez Ruixo (2)

Pharmacodynamic Modelling of Recombinant Human Erythropoietin Effect on Reticulocyte Production Rate and Age Distribution in Healthy Subjects

Thaddeus Grasela, PharmD, PhD

The Application of Systematic Analysis for Identifying and Addressing the Needs of the Pharmacometric Process

Callies Sophie, Andre Valerie, Vick Andrew-Mark, Graff Jeremy, Patel Bharvin, Brail Leslie, Lahn Michael

Modelling pharmacokinetic and pharmacodynamic properties of second generation antisense-oligonucleotides (ASOs).

Viera Lukacova, Walter S. Woltosz, Michael B. Bolger

PK/PD modeling of Adinazolam – effect of variability of absorption, PK and PD parameters on variability in PD response

C.M.T. Sherwin (1, 2), S. Svahn (3), A.J. Van Der Linden (4), N.J. Medlicott (2), R. Broadbent (1), D.M. Reith (1)

A pharmacokinetic/pharmacodynamic model to determine optimal dosing targets for amikacin in neonatal sepsis

Ng CM (1), Bauer RJ (2), Beeram M (1), Takimoto CH (1), Lin C (1), Patnaik A (1)

A Systematical Approach to Bridge the Two-Stage Parametric Expectation Maximization Algorithm and Full Bayesian Three-Stage Hierarchical Nonlinear Mixed Effect Methods in Complex Population Pharmacokinetic/Pharmacodynamic Analysis: Troxacitabine-induced Neutropenia in Cancer Patients

Pankaj Gupta, Matthew M Hutmacher, Bill Frame and Raymond Miller

A new approach for population pharmacokinetic data analysis under noncompliance

Bojan Lalovic, Matthew M Hutmacher, Bill Frame, Kaori Ito, Raymond Miller

Modeling the Dropout from Longitudinal Adverse Event Data: Selecting Optimal Titration Regimens

S. Hennig(1), R. Norris(2) C. M. J. Kirkpatrick(1)

Tobramycin in paediatric CF patients – TCI or “One dose fits all”

Stefaan Rossenu (1), Clare Gaynor (2), An Vermeulen (1), Adrian Dunne (2) and Adriaan Cleton (1)

A mixture distribution approach to IVIVC modeling of a dual component drug delivery system

J. Areberg, L.E. Broksø Kyhl

Simultaneous Population Pharmacokinetic Modelling of Parent Compound and Metabolite in Plasma and Urine for a New Drug Candidate

D. Hirt, F. Batteux, S. Urien, J.P. Richardet, P. Sogni, J. Poupon, A. Laurent, S. Pavlovic, M. Debray, J.M. Treluyer, B. Weill

Pharmacokinetic-pharmacodynamic modeling of manganese in patients with acute alcoholic hepatitis after an IV infusion of mangafodipir.

Ribba B., Tod M., Girard P., You B., Mercier C., Vassal G., Freyer G., Tranchand B.

ODE solvers and stiffness issues for complex population PK models

Dickinson GL (1), Dawson M (2), Ward TH (2), Danson S (3), Ranson M (2), Dive C (2), Aarons L (1).

Population pharmacokinetics of a novel anticancer drug, RH1, in terminal cancer patients.

Gijs Santen(1), Meindert Danhof(1), Oscar Della Pasqua(1,2)

Comparing treatment effect in depression trials: Mixed Model for Repeated Measures vs Linear Mixed Model

Fernandez-Teruel Carlos (1), Gonzalez-Alvarez Isabel (2), Navarro-Fontestad Carmen (2), Nalda-Molina Ricardo (3), Garcia-Arieta Alfredo (4), Bermejo-Sanz Marival (2), Casabo-Alos Vicente (2).

Simulations of bioequivalence trials using physiological-pharmacokinetic models with saturable and non-saturable hepatic clearance

M. Marchand (1), E. Fuseau (1), A.C. Heatherington (2), S. Sultana (2), P. R. Hidi (2), M. Boucher (2), P. Ellis (2), S.W. Martin (2)

Population PKPD modelling of biomarkers ANP and big ET-1 for two neutral endopeptidase inhibitors

C.Crepin(1), E.Fuseau(1), M.Portugal(2), D.Humilier(2)

Elimination of anti-epileptic compounds in Marseille aquatic environment from private hospital effluent – modelling versus measurements

M.A. Fabre (2), E. Fuseau (2), P. Cohen, H. Ficheux (1).

Selection of a dosing regimen with WST11 by Monte Carlo simulations, using PK data collected after single IV administration in healthy subjects and population PK modelling.

L. Alifrangis (1), P. André (2), R.V. Overgaard (1), C. Sola (2), A. Tisserant (2), N. Wagtmann (1), F. Romagne (2), S.H. Ingwersen (1).

Setting a Safe Starting Dose for a First-in-Man trial of a Monoclonal Antibody Based on Population PK-PD Predictions

Kayode Ogungbenro and Leon Aarons

Sample Size Calculations for Repeated Binary Population Pharmacodynamic Experiments

Daniël M. Jonker, Estelle Watson, Anders Dyhr Toft, Peter Kristensen, Lotte Bjerre Knudsen, Steen H. Ingwersen

Pharmacokinetic modelling of the once-daily human glucagon-like peptide-1 analogue, liraglutide, in healthy volunteers and comparison to exenatide

J. Bertrand (1), X. Panhard (1), A. Tran (2), E. Rey (2), S. Auleley (1), X. Duval (1, 3, 5), D. Salmon (4), J.M. Tréluyer (2), F. Mentré (1) and the COPHAR2- ANRS 111 study group

Influence of pharmacogenetic on pharmacokinetic interindividual variability of indinavir and lopinavir in HIV patients (COPHAR2 – ANRS 111 trial)

E. Plan, M. C. Kjellsson, M. O. Karlsson

Investigation of performances of FOCE and LAPLACE algorithms in NONMEM VI in population parameters estimation of PK and PD continuous data

E.K. Hansson(1), M. Sandström(2), H. Lindman(3), L.E. Friberg(1)

Modelling of Chemotherapy-induced Febrile Neutropenia using the Predicted Degree and Duration of Myelosuppression

Almond L1, Rowland Yeo K1, Howgate EM1, Tucker GT1,2, Rostami-Hodjegan A1,2

Mechanistic Prediction of HIV Drug-Drug Interactions in Virtual Populations from in vitro Enzyme Kinetic Data: Ritonavir and Saquinavir.

Marylore Chenel1, Kayode Ogungbenro2, François Bouzom1

Comparison of uniresponse and multiresponse approaches of PopDes to optimize sampling times for drug-drug interaction studies: application to a Servier compound.

Maria C. Kjellsson (1), Daniele Ouellet (2), Raymond Miller (2), Mats O. Karlsson (1)

Modelling Sleep Using Markov Mixed Effects Models

Gibiansky E. (1), J. Janik (2), D. Mahony (2), K. Kaucic (1), L. Hammershaimb (1), G. Robbie (1).

Population Pharmacokinetics of Siplizumab (MEDI-507): Implications for Dosing

Laffont CM (1), Mentré F (2) and Foos-Gilbert E (1)

Population pharmacokinetic analysis of perindoprilat in hypertensive paediatric patients

PLS Chan, E van Schaick, G Langdon, J Davis, T Parkinson, L McFadyen

PK-PD modelling to support go/no go decisions for a novel gp120 inhibitor

Bizzotto R, Nucci G, Poggesi I, Gomeni R

A Bayesian approach for the integration of preclinical information into a PBPK model for predicting human pharmacokinetics

S. Retout (1, 2), C. Bazzoli (1), E. Comets (1), H. Le Nagard (1), F. Mentré (1, 2)

Population designs evaluation and optimisation in R: the PFIM function and its new features

K. Petersson, E. Hanze, R.M. Savic, M.O. Karlsson

Semiparametric distributions with estimated shape parameters: Implementation and Evaluation

J.E. Wallin, L. E. Friberg and M. O. Karlsson

Predictive Performance of a Myelosuppression Model for Dose Individualization; Impact of Inter-Occasion Variability and Level and Type of Information Provided

Ivelina Gueorguieva and Kimberley Jackson

Prospective application of a multivariate population optimal design to determine parent and metabolite pharmacokinetic sampling times in a Phase II study.

L. McFadyen (1), P. Jacqmin (2), J. Wade (2), B. Weatherley (1)

Maraviroc Exposure Response Analysis: Phase 3 Antiviral Efficacy in Treatment Experienced HIV+ Patients

L. Iavarone(1), R. Gomeni(1), E. Merlo-Pich(2)

Population PK/PD of Alprazolam in the Attenuation of ACTH Activation Induced by Cognitive Performance in Metyrapone-treated Healthy Volunteers

C. Bazzoli (1), S. Retout (1, 2), F. Mentré (1, 2)

Population design in nonlinear mixed effects multiple responses models: extension of PFIM and evaluation by simulation with NONMEM and MONOLIX

Gianluca Nucci, Keith Muir and Roberto Gomeni

Population pharmacokinetic modelling of pimozide and its relation to CYP2D6 genotype.

A. Russu (1), M. Neve (2), G. De Nicolao (1), I. Poggesi (2), R. Gomeni (2)

Population methods for dose escalation studies: an MCMC approach

Paul G Baverel, Radojka M Savic, Justin J Wilkins, Mats O Karlsson,

Evaluation Of The Nonparametric Estimation Method In NONMEM VI: Application To Real Data

Antic, Julie (1,2) ; Chafaï, Djalil (1) ; Laffont, Céline (2) ; Concordet, Didier (1)

Evaluation of Non Parametric Methods for population PK/PD

Ihab G. Girgis, Vivek Viswanathan, Partha Nandy, and Surya Mohanty

Interactive Graphical Visualization Tool for Safety Data Screening

Marcella Petrone, Stefano Zamuner, Vincenzo Di Iorio, Roger Gunn, Marc Laruelle and Roberto Gomeni

Model-based sequential human PET study design for Optimal PK/RO assessment

Matthew M Hutmacher, Anand Vidyashankar, Debu Mukherhjee

Comparing Minimum Hellinger Distance Estimation (MHDE) and Hypothesis Testing to Traditional Statistical Analyses – a Simulation Study

Divya Menon (1), John T. Mondick (1), Bhuvana Jayaraman (1), Albert T. Cheung (2), Jeffrey S. Barrett (1)

Pharmacokinetics / Pharmacodynamics of Intravenous Bolus Nicardipine in Adults Undergoing Cardiovascular Surgery

Stacey Tannenbaum (1), Gene Williams (2), He Sun (3), I. Peter Lee (2), Lawrence Lesko (2), and Robert Temple (2)

A Comparison of Fixed Dose-Controlled (FD) versus Pharmacokinetic Modified Dose-Controlled (PKMD) Clinical Study Designs

Jeroen Schaap (1), Stefan Verhoeven (2), Gerard Vogel (3), Martijn Rooseboom (3,4) and Rene van Schaik (2)

Automation of Structural Pharmacokinetic Model Search in NONMEM: Evaluation with Preclinical Datasets

Anthe S. Zandvliet (1), Jan H.M. Schellens (2,3), William Copalu (4), Jantien Wanders (4), Mats O. Karlsson (5), Jos H. Beijnen (1,2), Alwin D.R. Huitema (1)

Phase I study design of indisulam: evaluation and optimization

Anthe S. Zandvliet (1), Jan H.M. Schellens (2,3), William Copalu (4), Jantien Wanders (4), Jos H. Beijnen (1,2), Alwin D.R. Huitema (1)

Dose individualization of indisulam to reduce the risk of severe myelosuppression

Emilie Hénin (1,2), Véronique Trillet-Lenoir (1,2,3), Olivier Colomban (1,2), Michel Tod (1,2), Pascal Girard (1,2)

Estimation of patient compliance from pharmacokinetic samples

Andreas Groth1, Judi Møss2, Tine Møller3, Steen Ingwersen1

A Population PK/PD Model Assessing The Pharmacodynamics Of A Rapid-Acting Recombinant FVII Analogue, NN1731, In Healthy Male Subjects

Sandra Visser(1), Elke Krekels(1), Kristina Ängeby Möller(2), Marie Angesjö(1), Ingemo Sjögren(1) and Odd-Geir Berge(2)

Modeling the time-course of the antipyretic effects and prostaglandin inhibition in relation the analgesic effects of naproxen: a compound selection strategy

Olofsen, E

The performance of model selection criteria in the absence of a fixed-dimensional correct model

I. Grabnar(1), B. Faganel(2), V. Dolzan(3), A. Mrhar(1), J. Jazbec(2)

Population Pharmacokinetics of Methotrexate in Children with Lymphoid Malignancy

K. Vucicevic(1), B. Miljkovic(1), M. Pokrajac (1), I. Grabnar(2)

Population Pharmacokinetic Modelling of Amitriptyline in Depression Patients

Martin Bergstrand, Elodie Plan, Maria Kjellsson, Mats O Karlsson

A comparison of methods for handling of data below the limit of quantification in NONMEM VI

F. Larsen (1), C. Bundgaard (2)

Non-Linear Mixed Effects PK/PD Modelling of Acute Autoinhibitory Feedback Effects of Escitalopram (ESC) on Extracellular Serotonin (5-HT) Levels in Rat Brain

Massimo Cella(1), Gijs Santen(1), Frederik Gorter de Vries(1),Meindert Danhof(1), Oscar Della Pasqua(1,2)

A model-based approach to dose selection in early paediatric development

Ricardo Nalda-Molina1, Belén Valenzuela(1), Arturo Soto-Matos(2), Bernardo Miguel-Lillo(2), Miguel Angel Izquierdo(2)

Population Pharmacokinetics of Aplidin® (plitidepsin) in Subjects with Cancer

RJ Keizer(1), E van Twuijver(2), JJ Marcar(2), PFW Strengers(2), ADR Huitema(1)

Bioequivalence study of a C1-esterase-inhibitor product (Cetor®) with optimised sampling design

Ramón-López A. (1), Nalda-Molina R. (1), Valenzuela B. (1), Pérez Ruixo J.J.(2)

Semi-mechanistic PKPD model for neutropenia using K-PD model in patients receiving high dose of chemotherapy

Aldaz A. (1), Sayar O. (1), Zufia L.(1), Viudez A.(2), Rifon J.(3), Nieto Y.(4)

Comparison between NONMEM and NPAG for gemcitabine modelling

Sayar O.(1), Aldaz A. (1),Zufia L.(1), Viudez A.(2), Rifón J.(3), Nieto Y.(4)

New model for gemcitabine and its metabolites

Mathilde Marchand (1, 2), Eliane Fuseau (1), David Critchley (3)

Supporting the recommended paediatric dosing regimen for rufinamide using clinical trial simulation

Mathilde Marchand (1, 2), Eliane Fuseau (1)

Predicting human from animal PBPK simulation combined with in vitro data

Robert Bauer(1), Serge Guzy(1), Hanna E Silber(2), Petra M Jauslin(2,3), Nicolas Frey(3), Mats O Karlsson(2)

Comparison between NONMEM and the Monte-Carlo Expectation Maximization (MC-PEM) Method Using a Physiologically-Based Glucose-Insulin Model

Zexun Zhou, Marc Pfister, and Amit Roy

Optimal Sampling Design and Trial Simulation using POPT and NONMEM

Jean-Marie MARTINEZ, David FABRE & Vanaja KANAMALURU

Population Pharmacokinetics of Rimonabant in Obesity

Robert R. Bies1, Serge Guzy2, Joshua Sokoloski3, Laura Drewencki3, and Amy K. Wagner3.

An MCPEM approach to understanding inter-animal and inter-treatment changes with in vivo striatal dopamine clearance in rats.

M.C. Peterson(1), M.M. Riggs(2)

Calcium Homeostasis and Bone Remodeling: Development of an Integrated Model for Evaluation and Simulation of Therapeutic Responses to Bone-Related Therapies

N.H. Prins(1), G. Graham(2), C. Muto(3), A. Pidgen(4)

Modeling of plasma aldosterone concentrations after prokinetic 5-HT4 receptor agonists: forming an integrated simulation framework for summary statistic and subject-level data.

Mahesh N. Samtani, Juan Jose Perez-Ruixo, Kathryn Brown, Dirk Cerneus, Christopher Molloy

PK/PD Model of Pegylated Thrombopoietin Mimetic Peptide in Healthy Subjects: Comparison of Verification Procedures for Assessing Model Predictability.

Hui Kimko, Steven Xu, Bindu Murthy, Mahesh Samtani, Partha Nandy, Richard Strauss, Gary Noel

Population Pharmacokinetic Analysis To Support Dosing Regimens Of Ceftobiprole

Marc Buyse

Validation of statistically reliable biomarkers

T Klitgaard , JN Nielsen, MS Fitsios, and M Lange

Population Pharmacokinetic Model for Human Growth Hormone in Adult Patients in Chronic Dialysis vs. Healthy Subjects

J. Grevel1, E. Fuseau1, C. Crepin1, M. Vernaz-Gris1, M. Marchand1, D. Huntjens2

Evaluation of the population pharmacokinetic properties of lidocaine and its metabolites, MEGX, GX, and 2,6-xylidine, after application of lidocaine 5% medicated plaster.

Lemenuel-Diot A., Laffont C.M. , Jochemsen R., Foos-Gilbert E.

Evaluation of model of Heart Rate during Exercise Tolerance Test with missing at random dropouts

Marc-Antoine Fabre, Eliane Fuseau(1), Maria-Laura Sargentini-Maier, Nathalie Toublanc(2)

Retrospective population pharmacokinetic analysis of seletracetam in epileptic and healthy adults