Efficacy of the Clinical Agent VT-1161 against Fluconazole-Sensitive and -Resistant Candida albicans in a Murine Model of Vaginal Candidiasis

摘要: Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) remain major health problems for women. VT-1161, a novel fungal CYP51 inhibitor which has potent antifungal activity against fluconazole-sensitive Candida albicans, retained its in vitro potency (MIC50 of ≤0.015 MIC90 0.12 μg/ml) 10 clinical isolates from or RVVC patients resistant to fluconazole 8 64 μg/ml). VT-1161 pharmacokinetics mice displayed high volume distribution (1.4 liters/kg), oral absorption (73%), long half-life (>48 h) showed rapid penetration into vaginal tissue. In murine model using yeast, doses as low 4 mg/kg significantly reduced the burden 1 days posttreatment (P < 0.0001). Similar efficacy was measured when an isolate highly (MIC but fully sensitive used. When partially moderately used, remained efficacious, whereas efficacious on day did not sustain posttreatment. Both agents were inactive treating infection with that demonstrated weaker (MICs 2 μg/ml fluconazole, respectively). Finally, plasma concentrations free predictive excess MIC values. These data support development potentially more treatment RVVC.