Indications
Omadacycline is specifically indicated for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults. These conditions are caused by microorganisms that are susceptible to omadacycline.
Pharmacodynamics
The pharmacodynamics of omadacycline demonstrate a dual capability, functioning as either bacteriostatic or bactericidal, contingent upon the specific organism. It exerts its antibacterial effect by disrupting bacterial protein synthesis while sparing DNA, RNA, and peptidoglycan biosynthesis. Notably, omadacycline offers advantages over traditional tetracycline antibiotics, as it remains effective against bacteria with tetracycline resistance mediated by efflux pumps, such as those encoded by the tet(K), tet(L), and tet(B) genes, and ribosomal protection proteins encoded by the tet(O) and tet(M) genes. However, it is still susceptible to resistance due to RNA mutations linked to tetracycline resistance.
Absorption
Omadacycline exhibits an average absolute oral bioavailability of 34.5%, with a mean time to peak plasma concentration (Tmax) of 2.5 hours post-oral administration. Upon repeated dosing, the drug displays an accumulation factor of 1.5. Although official guidelines suggest that food intake does not significantly affect the rate or extent of absorption, some data point to a possible decrease in bioavailability when omadacycline is taken after meals. Notably, after intravenous administration, the concentrations in alveolar cells and epithelial lining fluid are significantly higher-25.8 and 1.5 times, respectively-compared to plasma, underscoring its substantial pulmonary penetration.
Metabolism
Omadacycline is not subject to metabolic transformation in humans, which underscores its direct pharmacological activity in its administered form.
Mechanism of Action
Omadacycline exhibits its mechanism of action by precisely binding to the primary tetracycline binding site on the bacterial 30s ribosomal subunit. This binding effectively inhibits protein synthesis, thereby disrupting various cellular functions. Such disruption can lead to the cessation of bacterial growth or induce cell death, depending on the context.
