Cethromycinum
Cethromycinum Uses, Dosage, Side Effects, Food Interaction and all others data.
Cethromycinum is a 3-keto (ketolide) derivative of erythromycin A with an 11,12-carbamate group and an O-6-linked aromatic ring system. Cethromycinum represents a joint development effort by Abbott Laboratories, Taisho Pharmaceuticals, and Advanced Life Sciences, intended to be marketed under the trade name Restanza for the treatment of community-acquired pneumonia. However, after completing phase III clinical trials, it was deemed safe but not sufficiently efficacious by the FDA.
Since this time, cethromycin has received FDA orphan drug designations for the prophylactic treatment of anthrax inhalation, plague due to Yersinia pestis, and tularemia due to Francisella tularensis. It has also been investigated, by itself or together with zoliflodacin, for the treatment of gonorrhea, and was recently suggested as a possible treatment for liver-stage Plasmodium sporozoite infection.
Cethromycinum binds to the 50S subunit of the bacterial ribosome to inhibit both ribosome assembly and bacterial protein synthesis. Adverse effects such as diarrhea, nausea, vomiting, and headache may be due to off-target inhibition of molecules within mammalian cells.
| Trade Name | Cethromycinum |
| Generic | Cethromycin |
| Cethromycin Other Names | Cethromycin, Céthromycine, Cethromycinum, Cetromicina |
| Type | |
| Formula | C42H59N3O10 |
| Weight | Average: 765.945 Monoisotopic: 765.420045112 |
| Protein binding | Cethromycin displays 86.7 to 95.6% human plasma protein binding over a range of concentrations between 0.1 to 30.0 μg/ml. |
| Groups | Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Cethromycinum is a ketolide antibiotic with broad-spectrum activity against Gram-positive, Gram-negative, and atypical bacteria that may be useful for treating several conditions including community-acquired pneumonia, inhalation anthrax, plague, and tularemia.
Cethromycinum currently has no FDA-approved indications; it was granted orphan drug designation for the prophylactic treatment of inhalation anthrax in 2007 and for the prophylactic treatment of both plague due to Yersinia pestis and tularemia due to Francisella tularensis in 2009.
Cethromycinum is also used to associated treatment for these conditions: Plague caused by Yersinia pestis, Tularemia, Inhaled anthrax caused by Bacillus anthracis
How Cethromycinum works
Respiratory tract infections can be caused by numerous strains of bacteria, requiring careful consideration of treatment and antibiotics effective against a broad spectrum of potential pathogens. Cethromycinum, like other macrolide antibiotics, binds to the 23S rRNA of the 50S subunit of the bacterial ribosome. This binding, primarily mediated through regions II and V of the rRNA, occludes the peptide exit tunnel and inhibits bacterial protein synthesis. In addition, cethromycin is capable of binding to ribosomal intermediates during ribosome biogenesis, inhibiting the formation of functional 70S bacterial ribosomes. Due to the sequence and structural similarity of ribosomes between species, cethromycin displays broad-spectrum activity against diverse Gram-positive, Gram-negative, and atypical bacteria.
Toxicity
Toxicity information regarding cethromycin is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as diarrhea, nausea, vomiting, abdominal pain, and headaches. Symptomatic and supportive measures are recommended.
Food Interaction
No interactions found.Volume of Distribution
Cethromycinum given in five 150 mg oral doses had an apparent volume of distribution at the terminal elimination phase of 1433 ± 843 L, and an apparent steady-state volume of distribution of 1453 ± 997 L. The corresponding values for a 300 mg dose was 761 ± 293 L and 769 ± 272 L. Cethromycinum is known to accumulate in the epithelial lining fluid and alveolar cells, as well as within polymorphonuclear leukocytes.
Elimination Route
Cethromycinum displays non-linear absorption kinetics. In healthy adults administered 150 mg cethromycin orally once daily for five doses, the calculated Cmax, Tmax, and AUC0-24 values were 0.181 ± 0.084 μg/ml, 2.01 ± 1.30 hrs, and 0.902 ± 0.469 μg*h/ml, respectively. Similarly, the corresponding values for a 300 mg dose were 0.500 ± 0.168 μg/ml, 2.09 ± 0.03 hrs, and 3.067 ± 1.205 μg*h/ml, respectively.
In another study using a single oral dose of 150 mg cethromycin, the Cmax was 318 ± 161 ng/ml, the Tmax was 1.79 ± 0.50, the AUC0-24 was 1596 ± 876 ng*h/ml, and the AUC0-∞ was 1662 ± 907 ng*h/ml.
Half Life
Cethromycinum given in five oral doses of 150 or 300 mg has a plasma half-life of 4.85 ± 1.10 and 4.94 ± 0.66 hrs, respectively. A single oral dose of 150 mg produced a measured half-life of 5.66 ± 0.77 hrs.
Clearance
Cethromycinum clearance in patients receiving a once-daily oral dose of 300 mg is reported to be approximately 63 L/h.
Elimination Route
Cethromycinum is primarily excreted by the biliary route, with 87.2% of an initial dose recovered in feces and only 7.0% in urine. Unchanged cethromycin accounted for 35.7% of the radioactivity recovered in feces and an N-desmethyl metabolite for 39.8%; the remaining radioactivity was approximately evenly divided between three minor metabolites and a group of uncharacterized additional products.
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