Pharmacokinetics / Pharmacodynamics as a mean to improve the medical prescription of antibiotics

Mont-Godinne, 29-03-01

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Table of Contents

Pharmacokinetics / Pharmacodynamics as a mean to improve the medical prescription of antibiotics

The ideal antibiotic ...

Will it always be ideal ?

Main causes of antibiotic failures... Adapted from Pechère J.C., 1988, 1993, 1998

Pharmacokinetics / pharmacodynamics as a step towards an improved therapy...

Pharmacokinetics ...

Pharmacodynamics ...

Ce que veut (et doit obtenir) le clinicien ...

Ce que veut (et doit obtenir) le clinicien ...

Pharmacokinetics / Pharmacodynamics in drug development and evaluation of efficacy 

PK/PD in drug develop-ment A view from FDA

Are PK/PD important for efficacy / toxicity ?

Pharmacokinetic/ Pharmacodynamics and antibiotic resistance...

Are PK / PD important in resistance ?

PK / PD of antibiotics in 2001 ?

PK / PD for Seminfect ?

PK/PD parameters: a first sight

PK/PD parameters : a 2d sight

Pharmacokinetics / Pharmacodynamics

PK/PD patterns of antimicrobial activity (1 of 3) (after WA. Craig, 2000)

PK/PD patterns of antimicrobial activity (2 of 3) (after WA. Craig, 2000)

PK/PD patterns of antimicrobial activity (3 of 3) (after WA. Craig, 2000)

Pharmacokinetics / Pharmacodynamics in action ... 

Aminoglycosides : obtain a peak !

Pharmacokinetics / Pharmacodynamics in action ... 

Pharmacokinetics / Pharmacodynamics in action ... 

Pharmacokinetics / Pharmacodynamics in action ... 

?-lactams : remain at least 50 % of the time above the MIC...

Typical pharmacokinetics of a model ?-lactam *

Pharmacokinetics / Pharmacodynamics in action ... 

Improving ?-lactam efficacy by reducing the interval

Pharmacokinetics / Pharmacodynamics in action ... 

Pharmacokinetics / Pharmacodynamics in action ... 

Reducing ? - lactams interval: where can we go ? 

? - lactams by continuous infusion

Pharmacokinetics / Pharmacodynamics in action ... 

PK/PD of fluoroquinolones: role of the 24h-AUC MIC ciprofloxacin in hospital-acquired pneumonia

AUC / MIC ratio

PPT Slide

PPT Slide

PPT Slide

PPT Slide

Pharmacokinetics / Pharmacodynamics in action ... 

Pharmacokinetics / Pharmacodynamics in action ... 

24h-AUC / MIC as a tool to determine acceptable sensitivities to fluoroquinolones (p.o.)

The role of the peak for fluoroquinolones ...

Peak concentrations as a tool to determine acceptable sensitivities to fluoroquinolones (p.o.)

Combining it all …(Peak and 24h-AUC / MIC) as predictors of efficacy of FQ ...

Pharmacokinetics / Pharmacodynamics in action ...

But be careful to individual variations

But be careful to individual variations

Pharmacokinetics / Pharmacodynamics in action: adusting the dose of a FQ for an MIC

Pharmacokinetics / Pharmacodynamics in action ... 

Why would you not use low doses ?

Resistance: a global overview...

Mechanisms of resistance to fluoroquinolones 

PK/PD and antibiotic efflux pumps...

PK/PD and antibiotic efflux pumps… an example with RND...

Pharmacokinetics / Pharmacodynamics in action ... 

Peak concentrations as a tool to prevent the emergence of resistance (MPC)

Where are we in 2001 ?

PK / PD: do they help ?

PK / PD: do they help ?

PK / PD: do they help ?

and let us hope we have a bright future...

Author: Paul M. Tulkens 

Email: tulkens@facm.ucl.ac.be

Home Page: http://www.md.ucl.ac.be/seminfect/resume.htm