Abstracts - PAGE Meeting (Population Approach Group Europe)

Abstracts (105)

Diane Testart(1), Pascal GIRARD(1,4), Jean-Pierre Droz(2), Emilie Henin(1), Claude Ardiet(2), Sylvie Zanetta(3), Brigitte Tranchand(1,2)

PK-PD model compared with K-PD model to predict haematotoxicity induced by anticancer drugs.

M. Joerger(1,2) A.D.R. Huitema(1) H.J.G.D. van den Bongard(3) O. van Tellingen(4) P. Baas(2) J.H. Schornagel(2) J.H.M.Schellens(2,5) J.H. Beijnen(1,2,5)

Determinants of the pharmacokinetics of methotrexate and its metabolite 7-hydroxy-methotrexate following high-dose infusional methotrexate

Bruce Green (1,2) , Howard Lee (1), Nathan Lack (3), D Dale (3), G Calandra (3), Ron MacFarland (3), K Badel (3), W Liles (4), G Bridger (3), Carl Peck (1)

Use of an indirect effect model to describe the mobilization of progenitor cells induced by AMD3100

B. Gruwez (1), M. Tod (1,2), A. Dauphin (1)

A mathematical model for paroxetine antidepressant effect time course and its interaction with pindolol

Chenel M (1, 2), Ogungbenro K (1), Duval V (2), Laveille C (2), Jochemsen R (2), Aarons L (1)

Optimal blood sampling time windows for parameter estimation using a population approach: design of a Phase II clinical trial

M. C. Rosario (1), P. Jacqmin (2), P. Dorr (3), M. Westby (3), E. van der Ryst (3) C. Hitchcock (3) & S. Felstead (3)

Model-based drug development of a new anti-HIV drug

John Lukas1, Angeliki Andrioti2, Anastasios Zografidis2, Monica Rodriguez2, Erasmia Psimenou3

Pharmacokinetics- guided targeting of mycophenolate mofetil (MMF) in combination renal transplantation treatment confirms the need for dose reduction

G. Fliss (1), A. Staab (2), C. Tillmann (2), D. Trommeshauser (2), H.G. Schaefer (2), C. Kloft (1)

Development and evaluation of a population pharmacokinetic model for cilobradine, an If channel blocker

A. Strougo(1), L. Zuurman(1), C. Roy(2), J.-L. Pinquier(2), A.F. Cohen(1), J.M.A. van Gerven(1), R. Schoemaker(1)

PK and PK/PD Modelling of CNS Effects and Heart Rate After THC Administration in Humans

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

Modelling of the Hamilton Depression Rating Scale in Unipolar Depression Trials

D Hirt (1), S Urien (2), V Jullien (1), G Firtion (1), E Rey (1), G Pons (1), S Blanche (3), and JM Treluyer (1)

Jakob Ribbing, Joakim Nyberg and E. Niclas Jonsson

The Lasso – A Novel Method for Predictive-Covariate Modelling of Population Pharmacokinetics/Pharmacodynamics

R. Miller, D. Ouellet, P. Burger, B.W. Corrigan

Exposure-Response Analysis Using Time to Event Data: An Example Using Sleep Onset.

Adeline Samson (1), Xavière Panhard (1), Marc Lavielle (2) and France Mentré (1)

Generalisation of the SAEM algorithm to nonlinear mixed effects model defined by differential equations : application to HIV viral dynamic models

Armel Stockis (1) and Eric Snoeck (2)

Dose-response analysis of levetiracetam add-on treatment in patients with partial epilepsy

V. Jullien(1), J.M. Tréluyer(1), E. Rey(1), P. Jaffray(1), A. Krivine(1), L. Moachon(1), A Lillo-Le Louet(2), A. Lescoat(1), N. Dupin(1), D. Salmon(1), G. Pons(1), S. Urien(1).

Population pharmacokinetics of tenofovir in HIV-infected patients taking highly active antiretroviral therapy.

L.Reyderman (1), A. Shah(1), P.Statkevich(1)

Designing Sparse-Sampling Schemes for Population PK Study of a Highly Variable Drug.

D, Santos Buelga1, MM Fernandez de Gatta1, EV. Herrera2, A Dominguez-Gil1,3, MJ García1

Vancomycin population pharmacokinetic analysis in patients with hematological malignancies

Nick Holford

Simultaneous modelling of disease progression and time to event with NONMEM – likelihood ratio test criteria for random and informative dropout models and an evaluation of two methods affecting the quality of parameter estimates

Panhard X (1), Legrand M (1), Taburet AM (2), Diquet B (3), Goujard C (2), Mentré F (1) and the Cophar 1 – ANRS 102 study group

High Inter-Patient Variability of Pharmacokinetics of Lamivudine (LMV), Stavudine (STV) and Zidovudine (ZDV) in HIV-Infected Patients treated with HAART (Cophar 1 – ANRS 102 Study).

S. Y. A. Cheung, I. Gueorguieva and L. Aarons

Structural identifiability analysis of some semi-physiologically based and whole body physiologically based (WBPBPK) pharmacokinetic models.

M. Levi(1), C. Ng (2), J-M. Gries (1), B. Davies (1)

Population Pharmacokinetics of Rituximab in RA (Rheumatoid Arthritis) Patients: Combining two phase II studies

L. Bueno (1), C. Pitou (2), S. Glatt (2), D. de Alwis (2), I.F. Trocóniz (1)

Mechanistic PK/PD modelling for signal transduction modulators. Application to TGF-beta RI antagonists.

L. Claret (1), E.H. Cox (1), L. McFadyen (2), A. Pidgen (2), P.J. Johnson (2), S. Haughie (2), M. Boolell (2), R. Bruno (1)

Modelling and Simulation of the Telephone Sexual Activity Daily Diary (TSADD) Data of patients with female sexual arousal disorder (FSAD) treated with sildenafil (Viagra).

T. Lehr (1), C. Tillmann (2), A. Staab (2), R. Krug-Schmid (2), D. Trommeshauser (2), H.G. Schaefer (2), C. Kloft (1)

A new CNS active drug and its metabolite: a population pharmacokinetic analysis

T. Lehr (1), C. Tillmann (2), A. Staab (2), D. Trommeshauser (2), R. Binder (2), H.G. Schaefer (2), C. Kloft (1)

Assessment of the potency of a metabolite relative to the parent compound using a population PK/PD model for the inhibition of a neurotransmitter re-uptake transporter in mice

CE Staatz (1,2), C Byrne (1), AH Thomson (1,2).

Population pharmacokinetic modelling of gentamicin and vancomycin in patients with unstable renal function following cardiothoracic surgery

N. Rivas, D Santos Buelga, J. Santos Borbujo, MJ Otero, A. Domínguez-Gil1, MJ García

Population pharmacokinetics of lamotrigine in epileptic patients with data proceeding of therapeutic drug monitoring

Iñaki F. Trocóniz 1, Christiane Tillmann 2, Dirk Trommeshauser2, Matthias Klueglich3, Juliet Roberts4, Hans G. Schaefer2

A New Model to Describe the Bradycardic Effects of If channel blockers in Healthy Volunteers

E. Gibiansky(1), L. Gibiansky(2)

Population PK/PD model of GPI 15715 and GPI-derived propofol in sedation and comparison of PK/PD models for ordered categorical observations

Patrick Johnson (1), Byron Jones (1), Barbara Bogacka (2), Oleg Volkov (2)

Optimising PK sampling under the constraint imposed in later phase clinical trials

Nick Holford

The Visual Predictive Check – Superiority to Standard Diagnostic (Rorschach) Plots

Jeffrey Wald, Jagdev Sidhu, David Blum, and Marianne Silver

Model Based Insights to Lamotrigine for Pain Associated with Diabetic Peripheral Neuropathy

Nick Holford (1), Nick Fleischer (2)

Topical Corticosteroid Bioequivalence – An Evaluation of the FDA Guidance

Andreas Krause, Florilene Bouisset, Amy Racine

Modeling Discontinuation of Treatment in Non-Ignorable Situations

Brunhild Schiltmeyer, Willi Cawello, Dirk Kropeit, Rolf Horstmann

Population pharmacokinetics of the new antiepileptic drug lacosamide in healthy subjects with different age and gender

Justin J Wilkins (1), Fredrik Jonsson (1), Per-Henrik Zingmark (2), Patrick Lyden (3), E Niclas Jonsson (1)

Predicting recovery progression in acute stroke using the Barthel Index

Aristides Dokoumetzidis and Leon Aarons

Propagation of population PK and PD information using a Bayesian approach: dealing with non-exchangeability

Ivelina Gueorguieva, Leon Aarons, Karin M. Jorga and Malcolm Rowland

Population Optimal Design for Multivariate Response Pharmacokinetic Models

E. Pigeolet(1), P. Jacqmin(2), L. Sargentini-Maier(1) and A. Stockis(1)

Retrospective Population Pharmacokinetic Analysis of Levetiracetam in Westerner and Japanese Adults

PH Zingmark(1,2), M Kågedal (1), MO Karlsson(2)

Modelling a spontaneously reported side-effect by use of a Markov mixed-effects model

T.Tanigawa (1,2), T.Morikawa (2). H.To (2), S.Higuchi (2)

A population PK model for nifedipine coat-core tablet

S. Tannenbaum (1,2), Nick Holford (2,4), H. Lee (2,3), C. Peck (2), D. Mould (5)

A Novel Method for Simulation of Correlated Continuous and Categorical Variables Using A Single Multivariate Distribution

Jan Freijer, Inez de Greef - van der Sandt, Teun Post, Bart Ploeger.

Robust fitting of pharmacokinetic models to Phase II/III clinical trial data

H.M. Jones(1), M. Pantze(1), A. Rakhit(2), T. Lavé(1), K. Jorga(2), J-E Charoin(2)

Prediction of drug-drug interactions and their associated variability in human populations: Application to erlotinib and its coadministration with ketoconazole and rifampicin

Anna-Karin Hamberg (1), Marja-Liisa Dahl (1), Gabriella Scordo (1), Roberto Padrini (2), Martina Barban (2) and E. Niclas Jonsson (3)

Pharmacokinetic/Pharmacodynamic Modelling of the Anticoagulant Activity of Warfarin

Josep María Cendrós(1), Iñaki F. Trocóniz(2), Concepción Peraire(1), and Rosendo Obach(1)

Population pharmacodynamic modelling of lanreotide (Lan) autogel (ATG) in patients with acromegaly

T.M. Post(1), W. de Winter(1), J. DeJongh(1, 2), I. Moules(3), R. Urquhart(3), D. Eckland(3) and M. Danhof(1, 2)

Treatment Efficacy of Combination-Therapy based on a Mechanistic Characterisation of Disease Processes in Type 2 Diabetes Mellitus over a two-year period

Xuejun Chen, Suresh Mallikaarjun

Modeling of circadian effect on lung function in patients with chronic obstructive pulmonary disease

Demiana William Faltaos(1), Saïk Urien(1), Valérie Carreau(2), Marina Chauvenet(2), Jean Sebastian Hulot(1), Philippe Giral(2), Eric Bruckert(2), Philippe Lechat(1).

Use of an indirect effect model to describe the LDL Cholesterol lowering process by statins

S. Chantel(1), P.Y. Petit(2), P. Martin(1), D. Massignon(3), F. Saulnier(2), M. Benoist(2), S. Granger(2), P. Maire(4,5), R.W. Jelliffe(5), G. Aulagner(1)

Population pharmacokinetics of enoxaparin used for thromboembolism prophylaxis after total hip replacement

Sarayut Janmahasatian[1], Stephen B Duffull[1,5], Susan Ash[2], Leigh C Ward[3], Nuala M Byrne[4], Bruce Green[1,5]

A Semi-Mechanistic Model For Quantification Of Lean Body Weight

Sylvie Retout, Jean-Eric Charoin, Karin Jorga

Relevance of the use of population design evaluation and optimisation methods in the context of drug development projects in Roche

T. Lehr (1), C. Tillmann (2), A. Staab (2), H.G. Schaefer (2), C. Kloft (1)

Evaluation of an enterohepatic circulation model: predicting the influence of cholestyramine on the pharmacokinetics of meloxicam

E. Tousset(1), B. Vrijens (1,2), J.-M. Métry (1), J. Urquhart (1,3)

Non-Adherence to Prescribed Therapy is a Major Obstacle for Population PK/PD Studies

Elisabet Nielsen (1), Anders Viberg (1), Otto Cars (2) and Marie Sandström (1)

A Semi-Mechanistic Pharmacokinetic-Pharmacodynamic Model for Antibiotics

A. Henningsson(1), A. Sparreboom(2,3), W. J. Loos(3), J. Verweij(3), M. Silvander(4,5) and M. O. Karlsson(1)

Population Pharmacokinetic Model for Cremophor EL

C. Tillmann (1), H.G. Schaefer (1), T. Lehr (2), A. Staab (1)

Meloxicam for juvenile rheumatoid arthritis patients: Is dosing on a mg/kg body weight basis justified?

V. Piotrovsky

Indirect-response model for the analysis of concentration-effect relationships in clinical trials where response variables are scores

Colom H1, Farré MR2, Soy D3, Peraire C1, Cendros JM1, Pardo N.2,Torrent M.2, Domenech J1, Mangues MA2

Population pharmacokinetics of high-dose methotrexate in osteosarcoma pediatric patients.

Sylvie Retout, Emmanuelle Comets, Adeline Samson and France Mentré

Designs in nonlinear mixed effects models: application to HIV viral load decrease with evaluation, optimization and determination of the power of the test of a treatment effect

K.C. Carlsson(1), M. Bergjord(1), E.R. Moberg(2) and N.O. Hoem(1)

Bioavailability of gabapentin assessed by cumulative urine sampling compared with a model for the saturated absorption of gabapentin.

B. Knebel (1), T. Bergsma (2), L. Gibiansky (1), J.T. Hane (1), M.R. Gastonguay (1)

NMQual: A Tool to Automate Installation and Facilitate Qualification of NONMEM

A. Vermeulen, F. De Ridder

Population PK/PD modeling of supine heart rate after oral administration of a new candidate antipsychotic drug

Anne Chain, Lutz Harnisch, Oscar Della Pasqua

Separating Signal from Noise: PK/PD modelling of QT-interval prolongation

O. Pétricoul (1), V. Cosson (2), C. Crépin (1), E. Fuseau (1), D. Critchley (3)

Understanding the variability in clinical response to rufinamide, a new antiepileptic drug: a pooled PKPD analysis

Mathilde Marchand (1), David Critchley (2), Christa Nagy (2), and Eliane Fuseau (1)

The effect of rufinamide concentration on the QT interval in healthy subjects treated during 18 days with multiple ascending doses: a population PKPD analysis.

K.-H. Liesenfeld (1), J. Stangier (1), C. Garnett (2), C. Tillmann (1), I. Troconiz (3), H. Lee (2), H.G. Schaefer (1)

PK/PD-Modeling (PK/PD) and Clinical Trial Simulation (CTS) of Early Clinical Data of a New Oral Direct Thrombin Inhibitor (Dabigatran Etexilate)

Tamara van Steeg(1), Elke Krekels(1), Jan Freijer(3), Fiona Macintyre(2) Meindert Danhof(1) and Elizabeth C.M. de Lange(1)

The influence of an increase in plasma protein binding on the pharmacokinetics and pharmacodynamics of S(-)-Propranolol

M. Simeoni(1), P. H. Van Der Graaf(2), P. Milligan(2), D. Verotta(3), G. De Nicolao(1), M. Rocchetti(4), I. Poggesi(4)

Counting events: population approaches using NONMEM

Edginton, A.E., S. Willmann, W. Schmitt

Prediction of Clearance in Children Using a Combined Physiology-based and Enzyme Ontogeny Approach

Edginton, A.E., S. Willmann, W. Schmitt

Predicting pharmacokinetics in children using PK-Sim®

Germani M (1), Simeoni M (2), Rocchetti M (1), Van der Graaf PH (3), Salhi S (3), Milligan P (3), Poggesi I (1).

Implementation of variability in a physiologically-based pharmacokinetic approach for simulating the first-in-animal study.

C. Lia Liefaard (1), Yoshi Tagawa (1,2), Meindert Danhof (1,3), Rob A. Voskuyl (1,4)

Population Pharmacokinetic/Pharmacodynamic Analysis of Different Subunit Selective GABAergic Ligands in an Animal Model of Epilepsy

Andrew Hooker (1), William S. Kerwin (2) and Paolo Vicini (3).

Simultaneous population D-optimal designs for contrast enhanced MRI measurements of atherosclerotic plaque neovasculature.

Klaas P. Zuideveld (1) & Piet H. van der Graaf (2)

Agonist-antagonist interaction models with slope factor: implications of an alternative derivation

K. Brendel(1), E. Comets(1), C.Laveille(2), C. Laffont(2), F. Mentré(1)

Metrics based on objective function for external validation of a population pharmacokinetic model

Oleg Volkov

Patients’ Non-compliance with Drug Administration Times and Optimal Population Design in Pharmacokinetics.

S. Chantel(1), P. Martin(1), P.Y. Petit(2), D. Massignon(3), F. Saulnier(2), M. Benoist(2), S. Granger(2), P. Maire(4,5), R.W. Jelliffe(5), G. Aulagner(1)

Pharmacokinetics modelling and anti-Xa level simulation of enoxaparin used for venous thromboembolism prophylaxis after orthopaedic surgery

González-Álvarez I, Fernández-Teruel C, Navarro-Fontestad MC, Ruiz-Garcia A., Bermejo M, Casabó VG.

Pharmacokinetics and bioavailability of new ciprofloxacin derivative (CNV 97101) in rat: repercussion of precipitation in stomach.

David Hermann (1), Wenping Wang (2), Christine Falcoz (3), Daniel Hartman (1), Jaap Mandema (4)

Strategies to Improve Model-based Decision-making During Clinical Development

B Hamrén (1), H Ericsson (1), P Öhman (1), D Anzalone (1), Mats O. Karlsson (2)

A pooled population pharmacokinetic analysis of tesaglitazar in patients with type 2 diabetes or with manifestations of insulin resistance

Bengt Hamrén (1), Hans Ericsson (1), Peter Öhman (1), Ingrid Gause Nilsson (1) and Mats O. Karlsson (2)

Pharmacokinetic and pharmacodynamic modelling of the dual PPAR α/γ agonist tesaglitazar in patients with manifestations of insulin resistance

A. Quartino(1), M.O. Karlsson(1), A. Freijs(1), N. Jonsson(1), P. Nygren (3), J. Kristensen (2), E. Lindhagen (2) and R. Larsson (2)

Population Based Pharmacodynamics for In Vitro Drug Sensitivity Assays: Prediction of Model Based Parameters of Drug Activity and Relationship to Clinical Outcome

Annabelle Lemenuel-Diot and Christian Laveille

Use of Time-to-event analysis to qualify activity of Ivabradine durign exercise tolerance tests

Vincent Duval & Christian Laveille

Ivabradine and S18982 activities on heart rate: a population PK/PD analysis

Stefano Zamuner and Roberto Gomeni

Use population approach to characterize PK time-course with erratic absorption

Marc Lavielle (1) and France Mentré (2)

Estimation of population pharmacokinetic parameters of saquinavir in HIV patients and covariate analysis with MONOLIX

P Olsson Gislekog (1), P Jacqmin (1), JJ Perez Ruixo (2).

Population Pharmacokinetics of rHuEpo in Healthy volunteers.

P.L. Gambús (1), M.J. Garrido (2), J. Fernández-Candil (1), R. Valero (1), I.F. Trocóniz (2) and N. Fábregas (1)

Pharmacokinetics and Pharmacodynamics of Rocuronium bromide in patients undergoing brain surgery: Influence of chronic Phenytoin therapy

Miren K. Zamacona, Roberto Gomeni

Modelling time varying kinetics using time dependent feedback control on clearance

Valerie Cosson (1), Roberto Gomeni (1)

Modelling placebo response in depression using a mechanistic longitudinal model approach

Nabil Semmar, Nicolas Simon

Cluster analysis : an alternative method for covariate selection in population pharmacokinetics modeling

José Moltó(1), Marta Valle(2), Asunción Blanco(3), Meritxell DelaVarga(3), Cristina Miranda(1), José Miranda(1), Joan Costa(4), Manuel José Barbanoj(2), Bonaventura Clotet(1,3).

Population pharmacokinetics of lopinavir in HIV-infected adults receiving lopinavir/ritonavir

Gianluca Nucci 1, Regan Fong 2, David J. Carpenter 2, Roberto Gomeni 1

Population pharmacokinetics of paroxetine in the pediatric population

Emmanuelle Comets (1), Céline Verstuyft (2) and France Mentré (1)

Building a pharmacogenetic model to describe the pharmacokinetics of digoxin

D. Elsherbiny(1), S. Asimus(2), M. Ashton(2), U. S. H. Simonsson(1)

Population pharmacokinetics of S-mephenytoin and its metabolites S-nirvanol and S-4-hydroxymephenytoin in CYP2C19 poor, intermediate and extensive metabolizers.

A. Aldaz(1), L. Zufía(1), I. Aquerreta(1), A. Gúrpide(2), J. Giráldez(1).

Pharmacokinetics of paclitaxel in liver transplantation cancer patients

L. Zufía(1), A. Aldaz(1), A. Ortega(1), F. Calvo(2), J. Giráldez(1)

Tegafur and 5-Fluorouracil pelvic tissues concentrations in rectal cancer patients treated with preoperative chemoradiation. The processed sample stability investigation and their impact in the reability of data

H.E. Silber (1), P.M. Jauslin (1, 2), R. Gieschke (2), N. Frey (2), P. Vicini (3), U.S.H. Simonsson (1), M.O. Karlsson (1)