Pharmacokinetic/Toxicity properties of the new anti-staphylococcal lead compound SK-03-92

William R. Schwan, Jill M. Kolesar, M. Shahjahan Kabir, Edmund J. Elder, Jeffrey B. Williams, Rachel Minerath, James M. Cook, Christopher M. Witzigmann, Aaron Monte, Tricia Flaherty

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Because of the potential of a new anti-staphylococcal lead compound SK-03-92 as a topical antibiotic, a patch, or an orally active drug, we sought to determine its safety profile and oral bioavailability. SK-03-92 had a high IC50 (125 μg/mL) in vitro against several mammalian cell lines, and mice injected intraperiteonally at the highest dose did not exhibit gross toxicity (e.g., altered gait, ungroomed, significant weight loss). Single dose (100 μg/g) pharmacokinetic (PK) analysis with formulated SK-03-92 showed that peak plasma concentration (1.64 μg/mL) was achieved at 20–30 min. Oral relative bioavailability was 8%, and the drug half-life was 20–30 min, demonstrating that SK-03-92 is likely not a candidate for oral delivery. Five-day and two-week PK analyses demonstrated that SK-03-92 plasma levels were low. Multi-dose analysis showed no gross adverse effects to the mice and a SK-03-92 peak plasma concentration of 2.12 μg/mL with the presence of significant concentrations of breakdown products 15 min after dosing. SK-03-92 appeared to be very safe based on tissue culture and mouse gross toxicity determinations, but the peak plasma concentration suggests that a pro-drug of SK-03-92 or preparation of analogs of SK-03-92 with greater bioavailability and longer half-lives are warranted.

Original languageEnglish
Article numberA12
Pages (from-to)617-626
Number of pages10
Issue number4
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2015 by the authors.


  • Drug formulation
  • Pharmacokinetics
  • Safety testing
  • Staphylococcus

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)
  • Biochemistry
  • Microbiology


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