Disease relevance of Ravuconazole

• Of the drugs tested, ER-30346 was the most effective drug against systemic aspergillosis [1].
• In experimental murine models of pulmonary aspergillosis, candidiasis, and cryptococcosis, ER-30346 reduced the numbers of CFU in the lungs significantly compared with the numbers of CFU in the lungs of the controls (P < 0.05) [2].
• Efficacy of ravuconazole in treatment of mucosal candidosis in SCID mice [3].
• The maximum concentration of drug in plasma and the area under the concentration-time curve for ER-30346 showed good linearity over a range of doses from 2 to 40 mg/kg of body weight [1].
• Thus, ER-30346 shows efficacy in murine aspergillosis, candidiasis, and cryptococcosis models [2].

High impact information on Ravuconazole

• Here, we found both in vitro and in vivo antagonism between liposomal amphotericin B and ravuconazole in simultaneous treatment of experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits [4].
• Ravuconazole was active against Aspergillus spp., other hyaline filamentous fungi, black molds, and some Mucorales [5].
• Ravuconazole was active against the majority of fluconazole-resistant isolates; but for 102 of 562 (18%) resistant isolates, mainly Candida tropicalis, Candida glabrata, and Cryptococcus neoformans, ravuconazole MICs were > or =1 microg/ml [6].
• Ravuconazole showed linear plasma pharmacokinetics and a large volume of distribution while maintaining concentrations in plasma above the MIC throughout the dosing interval [7].
• Treatment groups consisted of rabbits treated with ravuconazole at 2.5 (RVC2.5), 5 (RVC5), and 10 (RVC10) mg/kg of body weight/day, rabbits treated with amphotericin B (AMB) at 1 mg/kg/day, or untreated controls [7].

Chemical compound and disease context of Ravuconazole

• A model of orogastric candidosis in SCID mice, which mimics disease seen in AIDS patients, was used to evaluate ravuconazole in comparison with fluconazole for treatment [3].
• We studied the antifungal activity of micafungin, a new echinocandin, in combination with ravuconazole, a second-generation triazole, against experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits [8].
• Although LY-303366 showed activity in this rabbit model of invasive aspergillosis, ravuconazole was the more active agent, comparable to amphotericin B [9].
• We studied the antifungal efficacy, safety, and pharmacokinetics of ravuconazole lysine phosphoester in escalating dosages for the treatment of invasive pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits [7].
• The newer triazoles, such as voriconazole, posaconazole and ravuconazole, are not yet approved for invasive candidiasis [10].

Biological context of Ravuconazole

• The ravuconazole free-drug AUC/MIC ratios were similar for all of the organisms studied (10 to 36; mean +/- SD = 20.3 +/- 8.2; P = 0.43) [11].
• Ravuconazole kinetics and protein binding were performed in neutropenic infected mice [11].
• We investigated the compartmental plasma pharmacokinetics and tissue distribution of ravuconazole following administration of its novel intravenous (i.v.) di-lysine phosphoester prodrug, BMS-379224 [12].
• RESULTS: Ravuconazole inhibited abscess formation and significantly decreased the viable cell counts in abscesses in comparison with the untreated group [13].
• Ravuconazole has shown efficacy in candidiasis in immunocompromised patients, and onychomycosis in healthy patients [14].

Anatomical context of Ravuconazole

• The concentrations of ravuconazole in rat uterus and lung tissues were 2-to 6 times higher than the corresponding blood concentrations [15].
• OBJECTIVE: To determine the effectiveness and safety of ravuconazole in the treatment of toenail onychomycosis [16].

Associations of Ravuconazole with other chemical compounds

• Both ravuconazole and voriconazole were very active against all Candida spp [17].
• Posaconazole and ravuconazole were more active than voriconazole against Rhizopus spp [18].
• In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum [1].
• We susceptibility tested 17 clinical isolates of Aspergillus fumigatus, for most of which MICs of itraconazole were elevated (MIC at which 50% of the isolates tested are inhibited, 16 microg/ml), against itraconazole, posaconazole, ravuconazole, and voriconazole [19].
• Germinated and nongerminated conidial suspensions for testing of susceptibilities of Aspergillus spp. to amphotericin B, itraconazole, posaconazole, ravuconazole, and voriconazole [20].

Gene context of Ravuconazole

• The activity of BMS-207147 was minimally affected by overexpression of the gene encoding the efflux pump MDR1, but MIC increases were observed with changes in ERG11 and with overexpression of the CDR transporter gene [21].
• These findings are consistent with the potential for ravuconazole to both inhibit and induce CYP3A isozymes [22].

Analytical, diagnostic and therapeutic context of Ravuconazole

• Concentrations of ravuconazole were determined by a validated HPLC method [12].
• Plasma, lung and uterus tissue of rats were taken at 1, 2, 4, 8, 12, 16, 24, 32, 48, 60, and 72 h (n = 5) after oral administration of 10 mg/kg of ravuconazole [15].
• Ravuconazole is a very potent and specific anti-T. cruzi agent in vitro but its in vivo activity in mice is limited, probably due to its unfavourable pharmacokinetic properties in this animal model [23].

References