Table of Contents
Pharmacodynamics as a tool to improve the antiinfective
therapy: from in vitro models to (some) large-scale clinical applications
Pharmacodynamics as a tool to improve the antiinfective
therapy: from in vitro models fo (some) large-scale clinical applications
What is research all about ?
Antibiotische behandelingen: Wat verlangt de clinicus
?
Farmacokinetiek
Microbiology
Farmacodynamie
What did the textbooks say about antibiotic dosages
and schedules in the 70’s ?
What are we going to discuss ?
Aminoglycosides in the 70’s ...
Aminoglycosides monitoring in the 70’s ...
Aminoglycosides toxicity in the 70’s - 80’s ...
Aminoglycoside toxicity is not linked to peak ...
What is the (likely) mechanism of aminoglycoside
nephrotoxicity ?...
Aminoglycoside entry in proximal tubular cells
is via brush border binding *...
Aminoglycoside accumulation is kidney is saturable
at clinically meaningful concentrations * ...
The once-a-day schedule gives less drug accumulation
and less renal alterations in rats * ...
Shall you now go to humans ?
Aminoglycoside once-a-day: the philosophy of the
first St Luc clinical trials (1985-1989) ...
Using surrogate markers ….
Phospholipiduria can be a surrogate marker of aminoglycoside-induced
renal alterations
High tone audiometry can be a surogate marker of
a clinically meaningful ototoxicity
Setting up the analysis scheme
Pharmacokinetic results (day 7)...
Phospholipiduria (1)
Phospholipiduria (2)
Phospholipiduria: statistical comment ...
Auditory alterations
Auditory alterations: statistical comment ...
Auditory alterations
General conclusions of the first clinical trials
… *
But, will once-a-day be effective ?
Aminoglycosidepeak /MIC ratio is predictive of
clinical efficacy
How are you going to show that patients will benefit
of receiving aminoglycosides once-a-day ?
The worldwide progress of the once-a-day made by
clinicians ...
The fluoroquinolones in 5 ? slides...
The fluoroquinolone problem...
PK/PD and antibiotic efflux pumps… an example with
RND...
Is pharmacodynamic important for fluoroquinolones
?
Act directly with the regulators ….
And look at the FDA registration dossier * of a
new fluoroquinolone...
But do not forget Belgium ...
Now, the ?-lactams
PK / PD in actie … continu infuus of ?-lactams
met 4 g /dag ...
Continu infuus van ? - lactamen in de praktijk:
farmaceutische aspecten ...
1ste toepassing : continu-infuus van ? - lactamen
in mucoviscidose
2de toepassing: continu-infuus van ? - lactamen
in intensieve zorgen
Degradation products of ceftazidime
Degradation pathways of ceftazidime
Cefatzidime compatibility (clinical conditions)
Now, where to run that study ...
Patients’enrollement: status report February 12th,
2001
PPT Slide
Pharmacodynamics...
Thanking people … *
Aminoglycosides...
Aminoglycosides... The once-a-day story...
The ?-lactams, the fluoroquinolones, etc...
But don’t forget ISAP...
And thanks to the Pharmacy and the * Pharmacists... |