Indications
Tedizolid Phosphate is indicated for the treatment of acute bacterial infections of the skin and skin structure (ABSSSI). For optimal effectiveness and to prevent the development of drug resistance, tedizolid should only be prescribed for infections confirmed to be caused by bacteria that are susceptible to the drug.
Pharmacodynamics
Tedizolid belong·he class of oxazolidinone antibiotics and functions by inhibiting·hesis in bacterial ribosomes. Although primarily targeting·have the potential to bind to human mitochondrial ribosomes, potentially leading·h as neurological, hematological, and gastrointestinal toxicity. However, tedizolid is generally better tolerated than its counterpart, linezolid. It is advisable to explore alternative treatments when managing·hea have been documented in patients undergoing·h tedizolid.
Absorption
Following·hieves peak plasma concentrations within approximately three hours, whereas intravenous administration results in peak levels within one hour. The oral bioavailability of tedizolid is notably high at around 91%, and food intake does not impact its absorption. Regardless of whether administered orally or via intravenous route, tedizolid reaches steady-state concentrations in approximately three days when dosed once daily. For oral administration, the maximum concentration (Cmax) is observed at 2.0 ± 0.7 mcg/mL after a sing·hereas for intravenous administration, these values are 2.3 ± 0.6 mcg/mL and 3.0 ± 0.7 mcg/mL, respectively. The time to reach maximum concentration (Tmax) is between 2.5 hours (rang·hours) and 3.5 hours (rang·hours) for oral administration, and approximately 1.1 hours (rang·hours) and 1.2 hours (rang·hours) with intravenous administration. The area under the curve (AUC) is reported as 23.8 ± 6.8 mcg*hr/mL for oral and 26.6 ± 5.2 mcg*hr/mL for intravenous dosing·hr/mL and 29.2 ± 6.2 mcg*hr/mL, respectively, at steady-state.
Metabolism
Tedizolid is administered as a phosphate prodrug, which is metabolized into its active form, tedizolid, upon administration. The primary metabolic pathway involves conversion to an inactive sulphate conjugate in the liver, largely independent of cytochrome P450 enzymes. This metabolic process facilitates the elimination of tedizolid from the body.
Mechanism of Action
Tedizolid Phosphate operates by targeting bacterial protein synthesis, addressing the challenge posed by multidrug-resistant organisms, such as methicillin-resistant Staphylococcus aureus. As part of the oxazolidinone class, it effectively overcomes resistance seen in other bacterial protein synthesis inhibitors. Protein synthesis is facilitated by ribosomes, which are complex structures composed of protein and ribosomal RNA (rRNA). These ribosomes operate through the peptidyltransferase center (PTC), utilizing the A, P, and E sites to catalyze peptide bond formation between amino acids carried by charged aminoacyl-tRNAs. The bacterial ribosome consists of a 30S small subunit and a 50S large subunit. Initially, it was believed that oxazolidinones, including linezolid and tedizolid, impeded an early stage of protein synthesis initiation. However, further research indicated that these compounds bind within the A site of the PTC, specifically interacting with the 23S rRNA element. This binding induces a conformational change in a conserved nucleotide (U2585 in Escherichia coli) within the 23S rRNA, rendering the PTC ineffective for peptide bond creation. Thus, tedizolid exerts its antibacterial effect by inhibiting essential bacterial protein synthesis.
