Pharmacokinetics / pharmacodynamics as a step towards a more effective therapy...

Monte-Carlo, February 14th, 2000

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Table of Contents

PPT Slide

Pharmacokinetics / pharmacodynamics as a step towards therapy...

PK/PD parameters: a first sight

What does the clinician (and the patient) want ?

Pharmacokinetics ...

Pharmacodynamics ...

Pharmacokinetic/ Pharmacodynamics in Drug Development and Evaluation of Efficacy (1/2)

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

Pharmacokinetic/ Pharmacodynamics in Drug Development and Evaluation of Efficacy (2/2)

Pharmacokinetic/ Pharmacodynamics and antibiotic resistance...

PK/PD and drug devlop-ment A view from EMEA

Pharmacokinetic/ Pharmacodynamics in Drug Development and Evaluation

Pharmacokinetic / Pharmacodynamic parameters: a 2d sight

PK/PD: role of concentration

PK/PD: role of concentration an example with Listeria monocytogenes

PK/PD: role of time 

PK/PD of FQ: in vitro dynamic models

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

How do you get a given 24h-AUC ? 1. importance of the dose (a)

How do you get a given 24h-AUC ? 1. importance of the dose (b)

How do you get a given 24h-AUC ? 1. importance of the dose (c)

How do you get a given 24h-AUC ? 2. importance of the clearance

Can you use 24h-AUC / MIC to optimize your therapy ?

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

Is 24h-AUC / MIC the only critical parameter ?

The role of the peak : animal models

Fq PK/PD : peak to MIC ratio in the clinic (1/2) 

Fq PK/PD : peak to MIC ratio in the clinic (2/2) 

Peak concentrations of the main fluoroquinolones (p.o.)

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

PK/PD : what do we need to do ?

Peak concentrations and 24h-AUC / MIC as predictors of efficacy...

But isn’t anything more about the peak ?

Could efficacy prevent the emergence of resistance ? 

The importance of double mutation ...

Mutant-prevention concentration (MPC) (1/3)

Bactericidal activity of FQs against M. bovis 

Mutant-prevention concentration (MPC) (2/3) ...

Role of the C8-methoxy in decreasing MPC

N-1-cyclopropyl-fluoroquinolones with a C8-methoxy

Peak concentrations as a tool to prevent emergence of resistance (MPC): accepting NCCLS breakpoints ...

Peak concentrations as a tool to prevent emergence of resistance (MPC): using “ PK / PD acceptable ” MICs

The design of the SUPERFLOXACIN... Pharmacokinetics / Pharmacodynamics...

A new fluoroquinolone for the year 2,000

Pharmacokinetics / Pharmacodynamics Will this really help ? 

And we may have a very bright future...

Author: Paul M. Tulkens 

Email: tulkens@facm.ucl.ac.be

Home Page: http://www.md.ucl.ac.be/facm/facm-conferences.htm