Intraocular penetration of systemically administered antifungal agents

Area of Science:

• Ophthalmology
• Mycology
• Pharmacokinetics

Background:

• Fungal endophthalmitis is a serious intraocular infection.
• Accurate drug levels in ocular tissues are crucial for effective treatment.
• Limited data exists on vitreous and aqueous humor concentrations of key antifungal agents.

Purpose of the Study:

• To quantify the levels of Amphotericin B, 5-flucytosine (5-FC), and ketoconazole in ocular fluids.
• To assess the penetration of these antifungals into the vitreous and aqueous humor in patients with fungal endophthalmitis.

Main Methods:

• Analysis of vitreous and aqueous humor samples from four patients with fungal endophthalmitis.
• Therapeutic vitrectomy was performed on all patients.
• Drug concentrations were determined using validated analytical methods.

Main Results:

• Low vitreous levels of Amphotericin B were observed (0.04 - 0.17 microgram/ml).
• One patient showed a high 5-flucytosine concentration (22.2 micrograms/ml) in ocular fluid.
• Ketoconazole demonstrated measurable levels in both aqueous (0.35 microgram/ml) and vitreous (0.71 microgram/ml) humor in one patient.

Conclusions:

• Amphotericin B penetration into the vitreous may be limited in fungal endophthalmitis.
• 5-flucytosine and ketoconazole show potential for achieving therapeutic concentrations in ocular tissues.
• Further studies are needed to optimize antifungal regimens for intraocular fungal infections.