Omadacycline

Absorption

Omadacycline has an mean absolute oral bioavailability of 34.5% and a mean Tmax of2.5 h with oral dosing. With multiple dosing, Omadacycline displays an accumulation factor of 1.5. Official labeling states that food does not significantly impact rate or extent of absorption, however, conflicting data exists suggesting food may lower the bioavailability of omadacycline taken after eating. The exposure in alveolar cells and epithelial lining fluid is 25.8 and 1.5 fold higher than plasma exposure after IV administration, suggesting Omadacycline penetrates the lungs to a significant degree.

Toxicity

No carcinogenicity studies have been conducted with Omadacycline, however, other tetracycline drugs have shown oncogenicity. Specifically, oxytetracycline increased incidence of adrenal and pituitary tumors and minocycline increased incidence of thyroid tumors.
Omadacycline has tested positive for clastogenicity and aneugenicity during in-vitro Chinese hamster ovary cell studies and for mutagenicity in mouse lymphoma cells. Both positive results occurred in the presence of metabolizing enzymes. Omadacycline has tested negative for chromosomal aberration of any kind during in-vitro Chinese hamster V79 cell testing. It has further tested negative during in-vivo micronucleus assays in ICR mice and HanRcc: WIST rats.
Omadacycline reduced sperm counts and sperm-motility in male rats at repeat dosages equivalent to 1.3 times the normal human exposure but produced no effect on fertility parameters. Inhibition of spermatogenesis was noted at repeat dosages equivalent to 6-8 times normal human exposure for a duration greater than 37 days but not at dosages under 2 times normal human exposure or durations of less than 4 weeks. Ovulation and embryonic survival was reduced in female rats at dosages approximating normal human exposure administered before mating through early pregnancy.
Thyroid hyperpigmentation, goitrogenicity, thyroid hyperplasia, and adrenal have been noted in multiple animal studies using other tetracycline drugs.

Description

Omadacycline, the drug that US FDA approved for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. It is not susceptible to common tetracycline-resistancemechanisms, and has demonstrated efficacy against a broad spectrum of pathogens including resistant isolates, which are increasing in prevalence and complexity.

The Uses of Omadacycline

Omadacycline is a potent an demonstrates efficacy against both Bacillus anthracis and Yersinia pestis; Also, it is a novel aminomethylcycline antibiotic in clinical development for community-acquired bacterial pneumonia (CABP).

Indications

Omadacycline is indicated for the treatment of community acquired bacterial pneumonia and acute bacterial skin and skin structure infections caused by omadacycline-susceptible organisms in adults.

Background

Omadacycline has been used in trials studying the treatment of Bacterial Pneumonia, Bacterial Infections, Community-Acquired Infections, and Skin Structures and Soft Tissue Infections. Omadacycline represents a significant advance over the well-known tetracycline family, and has been shown to be highly effective in animal models at treating increasingly problematic, clinically prevalent infections caused by gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), and by gram-negative, atypical and anaerobic bacteria, including those resistant to currently available classes of antibiotics and known to cause diseases such as pneumonias, urinary tract infections, skin diseases and blood-borne infections in both the hospital and community settings.

Definition

ChEBI: Omadacycline is a member of tetracyclines.

Pharmacokinetics

Omadacycline can be either bacteriostatic or bacteriocidal depending on the organism involved. It disrupts bacterial protein synthesis without affecting DNA, RNA, or peptidoglycan synthesis. Omadacycline represents an improvement over existing tetracycline agents as it has not been found to be subject to tetracycline resistance mediated by tetracycline efflux pumps encoded by the tet(K), tet(L), and tet(B) or to ribosomal protection proteins encoded by tet(O) and tet(M). Omadacycline is susceptible to RNA mutations which confer resistance to tetracyclines.

Pharmacology

Omadacycline has shown clinical efficacy in anaerobic acute bacterial skin and skin structure infections (ABSSSI) and in animal models of intra-abdominal anaerobic infections.The in vitro activity of Omadacycline against clinically relevant anaerobes was similar to that of tigecycline, with MIC90 values of 1 to 8 g/ml against Bacteroides spp, 0.5 g/ml against Clostridium difficile, Prevotella spp., and Porphyromonas asaccharolytica,1 g/ml against Peptostreptococcus spp, and 16 g/ml against Clostridium perfringens.

Side Effects

OMadacycline may cause serious adverse reactions including hypersensitivity reactions, tooth discoloration,Clostridioides difficile-associated diarrhea, and reversible inhibition of bone growth when administered during the second and third trimesters of pregnancy.Common adverse reactions include nausea, vomiting, infusion site reactions, alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased, hypertension, headache, diarrhea, insomnia, and constipation.Mild to moderate nausea and vomiting were the most frequent treatment-emergent adverse events in omadacycline (111 [30%] of 368 and 62 [17%] of 368, respectively) groups.

Metabolism

Omadacycline is not known to be metabolized in humans.