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. Author manuscript; available in PMC: 2016 Jun 30.
Published in final edited form as: Curr Opin Investig Drugs. 2005 Aug;6(8):845–853.
Study Type Effect Studied Experimental Model Result Reference
In vitro Activity. Susceptibility testing by
the macro dilution
reference method of the
National Center for
Clinical Laboratory
Standards (NCCLS).
In vitro inhibitory activity of SPA-S-843 against
Aspergillus sp was superior than that of amphotericin
B. While the activity against R oryzae, P variotti,
Penicillium sp and S schenkii were similar. The MFC
values were 12.53, 12.00 and 19.20 µg/ml against
Aspergillus sp, Penicillium sp and S schenkii,
respectively.
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In vitro Activity. Broth and agar
microdilution by the
NCCLS.
SPK-843 had significantly lower MIC values than
amphotericin B against S cerevisae, C tropicalis, C
neoformans and C glabrata. SPK-843 was most
fungicidal against C krusei, C tropicalis and C
albicans.
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In vitro Activity. Contact test and germ
tube inhibition test.
SPK-843 killed C albicans in 3 min. The best fungicidal
activity occurred in a medium with low electrical
conductivity (0.001 M buffer strength) and pH 5.8. The
activity of SPK-843 is associated with the induction of
greater cellular damage following increasing leakage
of K+. SPK-843 produced 80% leakage in 4 min, while
amphotericin B produced 35% in the same time.
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In vivo Activity. CD-1 mice intravenously
infected with C albicans.
The activity of SPK-843 was 2-fold higher than
D-AMPH at doses of 0.2 to 0.4 mg/kg/day for 5 days.
At 0.8 mg/kg/day for 5 days, SPK-843 completely
eradicated C albicans in eight out of ten mice, whereas
the same dose of D-AMPH had no effect.
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In vivo Efficacy. CD-1 mice infected with
5 × 106 C albicans
KSG-27 cells.
SPK-843 (0.25 mg/kg) reduced viable C albicans cell
count in the kidney to less than 1/100 of control on day
1. At the same dose, SPK-843 eradicated fungi by day
4 from 50 to 100% of mice, whereas amphotericin B
required a dose of 1 mg/kg to reach these eradication
levels.
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