التفاصيل البيبلوغرافية
| العنوان: |
Evaluation of voriconazole anti-Acanthamoeba polyphaga in vitro activity, rat cornea penetration and efficacy against experimental rat Acanthamoeba keratitis. |
| المؤلفون: |
Gueudry, Julie, Le Goff, Laetitia, Compagnon, Patricia, Lefevre, Sabine, Colasse, Elodie, Aknine, Camille, Duval, François, François, Arnaud, Razakandrainibe, Romy, Ballet, Jean Jacques, Muraine, Marc, Favennec, Loïc |
| المصدر: |
Journal of Antimicrobial Chemotherapy (JAC); Jul2018, Vol. 73 Issue 7, p1895-1898, 4p |
| مصطلحات موضوعية: |
IN vitro studies, PHARMACOKINETICS, ANTIBACTERIAL agents, ANTIFUNGAL agents, TROPHOZOITES, ACANTHAMOEBA keratitis, ANIMAL experimentation, COMPARATIVE studies, CORNEA, CULTURES (Biology), RESEARCH methodology, MEDICAL cooperation, MICROBIAL sensitivity tests, OPHTHALMIC drugs, ORAL drug administration, PROTOZOA, RATS, RESEARCH, EVALUATION research, ANTIPROTOZOAL agents, VORICONAZOLE, PHARMACODYNAMICS |
| مستخلص: |
Background: Acanthamoeba keratitis (AK) is a sight-threatening infectious disease. Its effective and safe medical therapy remains highly debated. Recently, voriconazole, a monotriazole with noted in vitro activity against a large variety of fungi, has been successfully used both topically and systemically to treat human AK cases.Objectives: To measure anti-Acanthamoeba polyphaga in vitro activity, anti-rat AK efficiency and rat cornea penetration of eye-drop and oral voriconazole.Methods: A. polyphaga was maintained in axenic cultures. In vitro, amoebicidal and cysticidal activities of voriconazole were measured using an XTT assay. AK lesions of Sprague Dawley rats were scored from grade 0 to grade 3. For 21 days, from day 7 post-infection, voriconazole (1% solution) eye drops were instilled or voriconazole was administered by gavage (60 mg/kg/day). After killing, superficial corneal epithelium scrapings were cultured and analysed by PCR, and eye-globe histology was performed. Cornea and plasma concentrations were determined using 2D HPLC separation and tandem MS.Results: In vitro, voriconazole inhibited trophozoite proliferation with an IC50 value of 0.02 mg/L and an IC90 value of 2.86 mg/L; no cysticidal effect was found. In AK rats, eye drops reduced clinical worsening from day 7 to day 14 post-infection and oral voriconazole was not effective. Voriconazole cornea concentrations were directly dependent on the frequency of eye-drop instillations, which resulted in lower plasma concentrations, whilst oral voriconazole resulted in lower cornea concentrations.Conclusions: Present data underline the need for high-frequency eye-drop instillation regimens for efficient AK therapy. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
