title: Characterization of Neurologic and Ophthalmologic Safety of Oral Administration of Tedizolid for Up to 21 Days in Healthy Volunteers.
abstract: BACKGROUND
  Antibacterials that inhibit protein synthesis may be associated with mitochondrial toxicity, manifested as serious optic or peripheral neuropathy or myelosuppression. Tedizolid is a novel oxazolidinone antibacterial that may have reduced the potential for mitochondrial toxicity.
  
  
  OBJECTIVE
  Based on the results of 2 studies (NCT01623401 and NCT00671814) conducted early in the tedizolid development program, what is the potential for drug-induced optic and peripheral neuropathies with tedizolid treatment?
  
  
  METHODS
  Two phase-1 studies were conducted in healthy volunteers. The first was an open-label study in which subjects received 200 mg of oral tedizolid phosphate once daily for 10 days. The second was a double-blind, placebo- and active-controlled, dose-escalating (multiple-administration) study in which subjects received 200, 300, or 400 mg of oral tedizolid phosphate once daily or 600 mg of oral linezolid twice daily or oral placebo for 21 days. Overall safety and tolerability were assessed, and extensive ophthalmologic and neurologic assessments were performed in both studies.
  
  
  RESULTS
  In these 2 studies in healthy subjects, tedizolid administered for up to 21 days was not associated with drug-related ophthalmologic or neurologic adverse events. Incidences of adverse events involving the eye or the nervous system were generally low, and no clinically meaningful changes in ophthalmologic or neurologic test results were recorded during either study.
  
  
  CONCLUSIONS
  Using an extensive battery of ophthalmologic tests and detailed neurologic clinical examination, there was no evidence of clinical or subclinical neurologic or ophthalmologic changes suggestive of peripheral or optic neuropathy in healthy volunteers who received therapeutic and supratherapeutic doses of oral tedizolid for periods of up to 21 days.
authors.affiliation: Merck & Co, Inc, Kenilworth, NJ.
authors.forename: Edward
authors.initials: E
authors.lastname: Fang
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Muñoz
authors.forename: Philippe
authors.initials: P
authors.lastname: Prokocimer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology*; D003391:Cranial Nerves / Q000187:drug effects* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005654:Fundus Oculi; D005684:Gait / Q000187:drug effects* / Q000502:physiology; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D009900:Optic Nerve / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D009901:Optic Nerve Diseases / Q000139:chemically induced; D010755:Organophosphates / Q000009:adverse effects / Q000494:pharmacology*; D010080:Oxazoles / Q000009:adverse effects / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000187:drug effects / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D000072776:Slit Lamp Microscopy; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D010755:Organophosphates; D010080:Oxazoles; C515040:tedizolid phosphate