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Tedizolid API Manufacturers & Suppliers

General Description:

Tedizolid, identified by CAS number 856866-72-3, is a notable compound with significant therapeutic applications. Drug-resistant bacteria, such as methicillin-resistant _Staphylococcus aureus_, vancomycin-resistant _Enterococcus faecium_, and penicillin-resistant _Streptococcus penumoniae_, represent a massive public health threat. Tedizolid is a member of the oxazolidinone class of antibiotics, which includes the previously approved and is generally effective against multidrug-resistant Gram-positive bacteria. Tedizolid is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and is generally more effective and more tolerable than . Tedizolid was approved by the FDA on June 20, 2014, for sale by Cubist Pharmaceuticals as tedizolid phosphate (SIVEXTRO®). This product is currently available as both an oral tablet and as a powder for intravenous injection.

Indications:

This drug is primarily indicated for: Tedizolid is indicated for the treatment of acute bacterial infections of the skin and skin structure (ABSSSI). To prevent drug resistance, tedizolid should only be used for infections that are caused by susceptible bacteria. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Tedizolid undergoes metabolic processing primarily in: Tedizolid is administered as a phosphate prodrug that is converted to tedizolid (the circulating active moiety). Prior to excretion, the majority of tedizolid is converted to an inactive sulphate conjugate in the liver, though this is unlikely to involve the action of cytochrome P450-family enzymes. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Tedizolid are crucial for its therapeutic efficacy: Tedizolid reaches peak plasma concentrations within three hours for oral administration and within one hour following intravenous administration; the absolute oral bioavailability is approximately 91%. Food has no effect on absorption. When given once daily, either orally or intravenously, tedizolid reaches steady-state concentrations in approximately three days. The C_max for tedizolid after a single dose/at steady-state is 2.0 ± 0.7/2.2 ± 0.6 mcg/mL for oral administration, and 2.3 ± 0.6/3.0 ± 0.7 mcg/mL for intravenous administration, respectively. Similarly, the T_max has a median (range) of 2.5 (1.0 - 8.0)/3.5 (1.0 - 6.0) hrs for the oral route and 1.1 (0.9 - 1.5)/1.2 (0.9 - 1.5) hrs when given intravenous. The AUC is 23.8 ± 6.8/25.6 ± 8.4 mcg\*hr/mL for oral and 26.6 ± 5.2/29.2 ± 6.2 mcg\*hr/mL for intravenous. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Tedizolid is an important consideration for its dosing schedule: Tedizolid has a half-life of approximately 12 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Tedizolid exhibits a strong affinity for binding with plasma proteins: Approximately 70 to 90% of tedizolid is bound to human plasma proteins. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Tedizolid from the body primarily occurs through: When given as a single oral dose, approximately 82% of tedizolid is excreted via the feces and 18% in urine. The majority is found as the inactive sulphate conjugate, with only 3% recovered unchanged. Over 85% of the elimination occurs within 96 hours. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Tedizolid is distributed throughout the body with a volume of distribution of: The volume of distribution for tedizolid following a single intravenous dose of 200 mg is between 67 and 80 L. In a study involving oral administration of 200 mg tedizolid to steady-state, the volume of distribution was 108 ± 21 L, while a single 600 mg oral dose resulted in an apparent volume of distribution of 113.3 ± 19.3 L. Tedizolid has been observed to penetrate the interstitial space of both adipose and skeletal muscle tissue and is also found in the epithelial lining fluid as well as in alveolar macrophages. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Tedizolid is a critical factor in determining its safe and effective dosage: Tedizolid has an apparent oral clearance of 6.9 ± 1.7 L/hr for a single dose and 8.4 ± 2.1 L/hr at steady-state. The systemic clearance is 6.4 ± 1.2 L/hr for a single dose and 5.9 ± 1.4 L/hr at steady-state. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Tedizolid exerts its therapeutic effects through: Tedizolid is an oxazolidinone antibiotic that works by inhibiting protein synthesis by bacterial ribosomes. However, oxazolidinone antibiotics can also bind to human mitochondrial, but not cytoplasmic, ribosomes. Mitochondrial protein synthesis inhibition is associated with adverse patient effects such as neurological, hematological, and gastrointestinal toxicity, although tedizolid is tolerated better than the related . Alternative therapies should be considered when treating neutropenic patients with ABSSSI. _Clostridium difficile_-associated diarrhea has been reported in patients treated with tedizolid. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Tedizolid functions by: Despite renewed efforts to combat the spread of antimicrobial resistance, multidrug-resistant organisms, including gram-positive bacteria such as methicillin-resistant _Staphylococcus aureus_, remain a threat. Oxazolidinones represent a relatively new class of antibacterials inhibiting protein synthesis that is generally capable of overcoming resistance to other bacterial protein synthesis inhibitors. Protein synthesis involves the action of ribosomes, multi-subunit complexes composed of both protein and ribosomal RNA (rRNA) substituents. Translocation along the length of a messenger RNA and concomitant protein synthesis involves the action of the A, P, and E sites of the peptidyltransferase centre (PTC), which accepts charged aminoacyl-tRNAs and catalyzes the formation of peptide bonds between them. The bacterial 70S ribosome comprises a small (30S) and a large (50S) subunit. Early studies into the mechanism of action of oxazolidinone antibiotics suggested that they inhibit a step in the initiation of protein synthesis. However, this mechanism was inconsistent with mapped resistance mutations, and later studies involving cross-linking and direct structural determination of the binding site revealed that oxazolidinones, including both and tedizolid, bind in the A site of the PTC by interacting with the 23S rRNA component. The structural studies also revealed that oxazolidinone binding alters the conformation of a conserved nucleotide in the 23S rRNA (U2585 in _Escherichia coli_), which renders the PTC non-productive for peptide bond formation. Hence, tedizolid exerts its effect through inhibiting bacterial protein synthesis. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Tedizolid belongs to the class of organic compounds known as phenylpyridines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyridine ring through a CC or CN bond, classified under the direct parent group Phenylpyridines. This compound is a part of the Organic compounds, falling under the Organoheterocyclic compounds superclass, and categorized within the Pyridines and derivatives class, specifically within the Phenylpyridines subclass.

Categories:

Tedizolid is categorized under the following therapeutic classes: Anti-Bacterial Agents, Anti-Infective Agents, Antibacterials for Systemic Use, Antiinfectives for Systemic Use, BCRP/ABCG2 Inhibitors, Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates, Oxazoles, Oxazolidinone Antibacterial. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Tedizolid include:

• Water Solubility: 0.1 mg/mL
• Melting Point: 256.8
• pKa: 1.8, 6.5