Erythromycin: spectrum of activity
Erythromycin: details of
acid the degradation
What have the chemists
done to
avoid acid-instability ?
What have the chemists
done to
avoid acid-instability ?
Did these modifications
change
anything else in PK ?
Did these modifications
change
anything else ?
Drug interactions with macrolides
The main problem due to interactions between some macrolides and the cytochrome P 450 system, especially the CYP3A subclass of enzymes | |
Finally results in lowered metabolism of CYP3A-dependent drugs | |
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drug azi clari diri ery josa mid roxi spira | |
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théophyllin 0 0 0 ++ + ND 0/+ 0 | |
ciclosporin ND ND ND +++ +++ +++ + 0 | |
carbamazepin ND 0/+ ND +++ + + 0/+ 0/+ | |
midazolam 0 ++ ND ++ ND ND + ND | |
warfarin 0 ND ND + ND ND 0 ND | |
terfenadin 0 ++ ND +++ 0/+ ND 0 ND | |
cisapride ND ++ ND ++ ++ ND ND 0 | |
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From Petitjean et al. N=undocumented | |
Mainly considered as a class-effect, resulting from what is known for erythromycin, except for spira and azithromycin | |
Basic indications of
(classical) macrolides
in a world of no resistance
But was has been the problem ?
Inhibition of Protein Synthesis (1)
Inhibition of peptidyl transferase activity |
Resistance: a semi-rational answer ...
Inhibition of Protein Synthesis (2)
Inhibition of peptidyl transferase activity |
MIC50 [µg/ml] of wild type and mutant strains
Telithromycin, the first ketolide, was designed to overcome erythromycin A resistance within Gram (+) positive cocci and take advantage of PK improvements of clarithromycin |
Pharmacokinetics of
telithromycin
(as submitted to the FDA; april 2001)
Pharmacodynamics of
telithromycin
(as based on FDA submission; april 2001)
Which are the sensivities of S. pneumoniae towards telithromycin in Belgium in 2000 ?
Macrolides: the 16 atoms family
Macrolides: the 16 atoms family