| Indication |
For the treatment of Pneumococcal infection, acute
sinusitis, acute bacterial tonsillitis, acute bronchitis and
bronchiolitis, lower respiratory tract infection and lobar
(pneumococcal) pneumonia. |
| Pharmacodynamics |
Telithromycin is a ketolide antibiotic which has an
antimicrobial spectrum similar or slightly broader than that of
penicillin. It is often used as an alternative in patients who have an
allergy to penicillins. For respiratory tract infections, it has better
coverage of atypical organisms, including mycoplasma. Telithromycin
prevents bacterial growth by binding to bacterial 50S ribosomal subunits
and interfering with bacterial peptide translocation and elongation. |
| Mechanism of action |
Telithromycin acts by binding to domains II and V of 23S rRNA of
the 50S ribosomal subunit. By binding at domain II, telithromycin
retains activity against gram-positive cocci (e.g. Streptococcus
pneumoniae) in the presence of resistance mediated by methylases (erm
genes) that alter the binding site at domain V. Telithromycin may also
inhibit the assembly of nascent ribosomal units. Compared to
erythromycin A, telithromycin binds to the 23S rRNA with 10 times
greater affinity in erythromycin-susceptible organisms and 25 times
greater affinity in macrolide-resistant strains. This increased binding
affinity may be conferred by the C11-12 carbamate side chain of
telithromycin. The side chain appears to maintain binding at domain II
in the presence of resistance mediated by alterations in domain V. |
| Absorption |
Absolute bioavailability is approximately 57%. Maximal
concentrations are reached 0.5 - 4 hours following oral administration.
Food intake does not affected absorption. |
| Volume of distribution |
|
| Protein binding |
60 - 70% bound primarily to human serum albumin |
| Metabolism |
Hepatic - estimated 50% metabolized by CYP3A4 and 50% metabolized independent of cytochrome P450 |
| Route of elimination |
The systemically available telithromycin is eliminated by multiple
pathways as follows: 7% of the dose is excreted unchanged in feces by
biliary and/or intestinal secretion; 13% of the dose is excreted
unchanged in urine by renal excretion; and 37% of the dose is
metabolized by the liver. |
| Half life |
Main elimination half-life is 2-3 hours; terminal elimination half-life is 10 hours |
| Clearance |
Not Available |
| Toxicity |
LD50>2000 mg/kg (PO in rats). Adverse effects are similar to
those of clarithormycin and erithromycin and include diarrhea, nausea,
vomiting, loose stools, abdominal pain, flatulence and dyspepsia. It may
also cause dizziness, headache and taste disturbances. |
