Journal article
Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92
Antibiotics (Basel), Vol.4(4), pp.617-626
12/01/2015
DOI: 10.3390/antibiotics4040617
PMCID: PMC4748848
PMID: 26877886
Abstract
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 IC
50
(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.
Details
- Title: Subtitle
- Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92
- Creators
- William R. Schwan - University of Wisconsin–La CrosseJill M. Kolesar - University of Wisconsin Carbone Cancer CenterM. Shahjahan KabirEdmund J. Elder - University of Wisconsin–MadisonJeffrey B. WilliamsRachel Minerath - University of Wisconsin–La CrosseJames M. Cook - University of Wisconsin–MilwaukeeChristopher M. Witzigmann - University of Wisconsin–MilwaukeeAaron Monte - University of Wisconsin–La CrosseTricia Flaherty - University of Wisconsin–La Crosse
- Resource Type
- Journal article
- Publication Details
- Antibiotics (Basel), Vol.4(4), pp.617-626
- Publisher
- MDPI
- DOI
- 10.3390/antibiotics4040617
- PMID
- 26877886
- PMCID
- PMC4748848
- ISSN
- 2079-6382
- eISSN
- 2079-6382
- Language
- English
- Date published
- 12/01/2015
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984696538802771
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