NONMEM Users Network Archive

Hosted by Cognigen

Monoclonal antibodies QSP PhD proposal in CNRS, France

From: Nicolas Azzopardi <nicolas.azzopardi>
Date: Tue, 26 Apr 2016 12:27:16 +0200 (CEST)

Dear all,

I would like to share this opportunity for a PhD student in our laboratory =
for a 3 years period.
Our team is part of the National center for scientific research (CNRS), and=
 is involved in quantitative systems pharmacology of monoclonal antibodies.=
Below the general conditions and qualifications for the candidates.

Thanks in anticipation for circulating this opportunity.

Nicolas Azzopardi

PhD proposal

Location : University of Tours (France)

    * Informations:

Name of the supervisor: Denis Mulleman

Laboratory: CNRS UMR7292 (GICC)

Team : PATCH (PhArmacology of TherapeutiC antibodies in Human)

Co-supervisor : David Ternant

    * Short title: quantitative systems pharmacology of monoclonal antibodi=
es in rheumatoid arthritis

    * Summary:

Quantitative systems pharmacology is a mathematical approach to study the e=
ffect of drugs in a quantitative and dynamic manner. Gathering heterogeneou=
s data such as in vivo , preclinical, ex vivo and clinical data, it provide=
s a deep biological insight into a disease pathophysiology and a holistic u=
nderstanding of the mechanisms of action of drugs, from cellular to macrosc=
opic levels. It helps in quantifying the factors that may improve, or impai=
rs, therapeutic response. Quantitative system pharmacology may contribute i=
n precision medicine through a sound analysis and simulation approach, prov=
iding a basis for designing dose adjustment, according to individual patien=
t’s characteristics.

Inflammation, through its micro and macroscopic components, is likely to mo=
dulate the response to monoclonal antibodies that are used in immune-mediat=
ed inflammatory diseases. An analysis of the dose-response relationship, ba=
sed on mathematical modeling of both dose-concentration (pharmacokinetic) a=
nd concentration-response (pharmacokinetic-pharmacodynamic or PK-PD) relati=
onships, should decipher and quantify the interactions between inflammation=
 and response to monoclonal antibodies. Building a multi scale pathophysiol=
ogic system ( systems biology ), in combination with a pharmacokinetic and =
PK-PD model, quantitative system pharmacology should help in understanding =
the mechanism of action of monoclonal antibodies in immuno-inflammatory dis=

    * Key words: Inflammation, Monoclonal antibodies, Systems biology, Biom=
arkers, pharmacokinetics, PK-PD modelling, quantitative system pharmacology=
, rheumatoid arthritis

    * Five publications of the supervisor and co-supervisor during the last=
 4 years:

    * Ternant D, Ducourau E, Fuzibet P, Vignault C, Watier H, Lequerré=
 T, Le Loët X, Vittecoq O, Goupille P, Mulleman D, Paintaud G. Pharmac=
okinetics and concentration-effect relationship of adalimumab in rheumatoid=
 arthritis. Br J Clin Pharmacol. 2015;79:286-97.
    * Ducourau E, Ternant D, Lequerré T, Fuzibet P, Le Loët X, Wa=
tier H, Goupille P, Paintaud G, Vittecoq O, Mulleman D. Towards an individu=
alised target concentration of adalimumab in rheumatoid arthritis. Ann Rheu=
m Dis. 2014;73:1428-9.
    * Ternant D, Ducourau E, Perdriger A, Corondan A, Le Goff B, Devauchell=
e-Pensec V, Solau-Gervais E, Watier H, Goupille P, Paintaud G, Mulleman D. =
Relationship between inflammation and infliximab pharmacokinetics in rheuma=
toid arthritis. Br J Clin Pharmacol. 2014;78:118-28.
    * Mélet J, Mulleman D, Goupille P, Ribourtout B, Watier H, Thibaul=
t G. Rituximab-induced T cell depletion in patients with rheumatoid arthrit=
is: association with clinical response. Arthritis Rheum. 2013;65:2783-90.=
    * Edupuganti SR, Eder V, Ternant D, Courtehoux M, Tranquart F, Goupille=
 P, Paintaud G, Mulleman D. F-18 fluorodeoxyglucose positron emission tomog=
raphy can detect early response to adalimumab, a tumor necrosis factor-=
antagonist, in rheumatoid arthritis: A prospective pilot study. Joint B=
one Spine. 2015;82:381-3.

    * Eligibility criteria:

Master degree in quantitative system pharmacology
    2. Acquaintance with PK-PD modelling and simulation softwares
    3. Fluency with written and spoken English (mandatory)

    * Selection procedure: The best-qualified applicants will be invited lo=
cally for an interview by the Selection Board of the University.

    * Submission of applications: Candidates are requested to submit their =
application (cover letter + CV) to: Ms. Anne Mychak via email ( anne.mychak=
ecine, Bâtiment Vialle, 10 Boulevard Tonnellé, BP 3223, 37032 Tou=
rs Cedex 01 - FRANCE)

    * Dead line for application: June 1st, 2016

    * Starting date: September 2016, three years duration

Received on Tue Apr 26 2016 - 06:27:16 EDT

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to:

Once subscribed, you may contribute to the discussion by emailing: