My Profile

Search abstracts

Lewis Sheiner


2017
Budapest, Hungary



2016
Lisboa, Portugal

2015
Hersonissos, Crete, Greece

2014
Alicante, Spain

2013
Glasgow, Scotland

2012
Venice, Italy

2011
Athens, Greece

2010
Berlin, Germany

2009
St. Petersburg, Russia

2008
Marseille, France

2007
KÝbenhavn, Denmark

2006
Brugge/Bruges, Belgium

2005
Pamplona, Spain

2004
Uppsala, Sweden

2003
Verona, Italy

2002
Paris, France

2001
Basel, Switzerland

2000
Salamanca, Spain

1999
Saintes, France

1998
Wuppertal, Germany

1997
Glasgow, Scotland

1996
Sandwich, UK

1995
Frankfurt, Germany

1994
Greenford, UK

1993
Paris, France

1992
Basel, Switzerland



Printable version

PAGE. Abstracts of the Annual Meeting of the Population Approach Group in Europe.
ISSN 1871-6032

Reference:
PAGE 24 (2015) Abstr 3408 [www.page-meeting.org/?abstract=3408]


PDF poster/presentation:
Click to open Click to open

Poster: Drug/Disease modeling - CNS


IV-11 Mats Magnusson Population Pharmacokinetic Modeling of Paliperidone Palmitate 3-Month Formulation

Mats O. Magnusson (1)*; Mahesh N. Samtani (2)*; Elodie L. Plan (1); E. Niclas Jonsson (1); Stefaan Rossenu (3); An Vermeulen (3) (*equal contribution)

(1) Pharmetheus, Uppsala, Sweden; (2) Johnson & Johnson Pharmaceutical Research & Development, L.L.C., NJ, USA (3) Johnson & Johnson Pharmaceutical Research & Development, a Division of Janssen Pharmaceutical N.V., Beerse, Belgium

Background: A new paliperidone palmitate 3-month formulation (PP3M) has been developed aiming at retained efficacy compared to the marketed paliperidone 1-month formulation (PP1M).

Objectives:  To characterize the dose-concentration-time relationship of paliperidone following administration of PP3M.    

Methods:  Pharmacokinetic (PK) data were obtained from 1 single-dose Phase 1 study (R092670-PSY-1005) and 1 repeated-dose Phase 3 study (R092670-PSY-3012). Plasma concentrations were analyzed using non-linear mixed-effects PK modeling implemented in NONMEM 7.3.0 [1]. A previously developed PK model for PP1M was used to describe the PK of paliperidone after PP1M administration [2] for patients in Study R092670-PSY-3012 who were treated with PP1M for 4 months before PP3M treatment commenced. The final model for PP3M was based on 8990 PK samples from 651 subjects. 

Results:  The PP1M PK model provided an adequate description of the PP1M data when the model parameters were associated with uncertainty [3] (10%). A 1-compartment model with 2 saturable absorption processes (slow and fast) was developed to characterize the PK of paliperidone after PP3M administration. The covariates in the PP3M model were creatinine clearance on clearance, BMI on volume of distribution, injection volume on the absorption rate, and injection site and sex on the maximal absorption rate for the slow saturable absorption process. 

Conclusions:  The PK characteristics of paliperidone when administered as a single and multiple injections of PP3M were well captured in a population PK model for PP3M.    



References:
[1]  Beal SL, Sheiner LB, Boeckmann AJ & Bauer RJ (Eds.) NONMEM Users Guides. 1989-2011. Icon Development Solutions, Ellicott City, Maryland, USA.    
[2]  Samtani MN, Gopal S, Gassmann-Mayer C, Alphs, L, and Palumbo J M; Dosing and switching strategies for paliperidone palmitate: based on population pharmacokinetic modelling and clinical trial data. CNS Drugs, 25(10):829–845, Oct 2011.
[3] Gisleskog, P. O., Karlsson, M. O., and Beal, S. L. Use of prior information to stabilize a population data analysis. J Pharmacokinet Pharmacodyn, 29(5-6):473–505, Dec 2002.