Pharmacokinetics and Safety of Single-dose Tedizolid Phosphate in Children 2 to <12 Years of Age

Antonio C. Arrieta, Jocelyn Y. Ang, Claudia Espinosa, Oleksandr Fofanov, Camilla Tøndel, Margaret Z. Chou, Carisa S. De Anda, Jason Y. Kim, Dan Li, Philip Sabato, Pamela S. Sears, John S. Bradley

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Infections with Gram-positive bacteria, including acute bacterial skin and skin structure infections (ABSSSIs), are common in children. We describe a single-dose pharmacokinetics and safety study of tedizolid phosphate, a new oxazolidinone under investigation for the treatment of ABSSSIs in children, in hospitalized participants 2 to <12 years of age. Methods: This open-label, multicenter, phase 1 trial (NCT02750761) enrolled hospitalized children 2 to <12 years of age receiving treatment for a confirmed/suspected Gram-positive bacterial infection. Participants were stratified by age (2 to <6 years and 6 to <12 years) to receive a single oral or intravenous dose of tedizolid phosphate. Evaluations included safety and pharmacokinetics of tedizolid phosphate and its active metabolite, tedizolid. Palatability of the oral suspension was also evaluated. Results: Thirty-two participants were enrolled and received 3-6 mg/kg of study medication. For both routes of administration, tedizolid phosphate was rapidly converted to tedizolid; median time to maximum tedizolid plasma concentration was 1-2 hours after initiation of the 1-hour intravenous infusion and 2-3 hours after oral dosing. The tedizolid mean terminal half-life was 5-6 hours and 6-7 hours for the intravenous and oral administration groups, respectively. The oral tedizolid phosphate suspension demonstrated high bioavailability comparable to that of the parenteral administration. A single dose of intravenous or oral tedizolid phosphate was well tolerated; no unexpected safety findings were observed. Conclusions: Pharmacokinetic and safety observations provide the information necessary for the continued development of tedizolid phosphate for the treatment of Gram-positive infections in children, particularly ABSSSIs.

Original languageEnglish
Pages (from-to)317-323
Number of pages7
JournalPediatric Infectious Disease Journal
DOIs
StateAccepted/In press - 2021

Keywords

  • Gram-positive bacterial infections
  • methicillin-resistant Staphylococcus aureus
  • staphylococcal skin infections

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