Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92
AbstractBecause 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. View Full-Text
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Schwan, W.R.; Kolesar, J.M.; Kabir, M.S.; Elder, E.J.; Williams, J.B.; Minerath, R.; Cook, J.M.; Witzigmann, C.M.; Monte, A.; Flaherty, T. Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92. Antibiotics 2015, 4, 617-626.
Schwan WR, Kolesar JM, Kabir MS, Elder EJ, Williams JB, Minerath R, Cook JM, Witzigmann CM, Monte A, Flaherty T. Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92. Antibiotics. 2015; 4(4):617-626.Chicago/Turabian Style
Schwan, William R.; Kolesar, Jill M.; Kabir, M. S.; Elder, Edmund J.; Williams, Jeffrey B.; Minerath, Rachel; Cook, James M.; Witzigmann, Christopher M.; Monte, Aaron; Flaherty, Tricia. 2015. "Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92." Antibiotics 4, no. 4: 617-626.