According to an in vivo
model of infections in mice, macrolides can be seperated into two classes. First
is time above MIC for some macrolides such as erytromycin A, clarithromycin and
rodixromycin. Second is concentration-dependent killing for azithromycin.
Applying the same way, it is demonstrated
that using the area under the serum concentrations
to MIC ratio (AUC/MIC), the best correlation is acquired without regarding the
sensitivity of S. pneumoniae strains to erythromycin A.
The pharmacokinetic characteristics
of telithromycin has been defined in patients after single or repeated oral
doses of 800 mg. Thus metabolism and drug interactions of telithromycin has
After a 800 mg of telithromycin, in one hour
the mean peak plasma concentration (Cmax) was 1.9 mg/L. After
dosing,the plasma concentration was 0.03 mg/L at 24 hour. The mean area under
the curve (AUC) was 8.4 mg.h/L, and the terminal half-life ranges from 10 to 12 hour. Repeating
the doses during 10 days, using the AUC ratio, the mean accumulation ratio
calculated as 1.5.
Telithromycin is bound to serum proteins,
approximately 70% of the molecule is protein bound. The main protein involved
is human serum albumin (45-49%), accounting for a concentration of 2.4 mg/L,
with ?1-acid glycoprotein (12-30%) and liporoteins being responsible
fort he remaining part.
big part of the metabolism is made by the cytochrome P450 3A4 system, and the
other part is made by cytochrome P450-independent mechanisms. Of the systemically
available drug, 7% is excreted in the feces, 13% is excreted in the urine, and
37% is metabolized by the liver.
There is an increase in renal
elimination in patients with hepatic insufficiency. But, patients that have
hepatic impairment and renal impairment ,
the dosage should be decreased to half of the previous dosage.
The availability of multiple routes of elimination
reduces the impact of isolated renal or hepatic insufficiency on drug
accumulation. Higher intracellular concentrations of telithromycin can help for
curing intracellular pathogens.