Potentiation of Voriconazole (VCZ) Ocular Penetration by Topical Latanoprost (LT) Co-Administration

W. E. SPONSEL1, V. BERNALL1, G. PARIS2, Y. TRIGO1, M. PENA1, R. GLICKMAN1, J. R. GRAYBILL1

Author address: 

1The Univ. of TX Health Sci. Ctr. at San Antonio, San Antonio, TX, 2The Univ. of Tx Health Sci. Ctr. at San Antonio, San Antonio, TX

Abstract: 

Background: Fungal keratitis may rapidly progress to endophthalmitis. Topical antifungals may be inadequate to prevent this. We investigated potential enhancement of triazole penetration (Voriconazole; Pfizer) using the PGF2-alpha analogue latanoprost (Xalatan; Pharmacia & Upjohn). Methods: Five New Zealand rabbits were given one drop of 50 mcg/ml (2.5 mcg) of LT topically in the right eye daily for five days. The control left eye was given one drop of saline daily for five days. On day 6, the rabbits were sedated and a single 0.03 ml dose of 5 mg/ml methylcellulose suspension containing 150 mcg VCZ was injected into the subconjunctival space of both eyes. Rabbits were sacrificed after 70 min, and the eyes enucleated and dissected. Aliquots of aqueous humor were analyzed by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS, ThermoQuest LCQ) to determine the concentration of voriconazole. Results: Insufficient aqueous was obtained from one animal; results are based on the analysis of four rabbits. In three LT-treated eyes, VCZ in the aqueous humor ranged from 1.1 to 73.5 ng/ml, and was undetectable in one of the latanoprost-treated eyes. In the contralateral eyes, which had received identical doses of VCZ but without the preceding LT treatment, there was no detectable VCZ in three eyes, and only a trace amount (
2001

abstract No: 

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Full conference title: 

ICAAC 41st
    • ICAAC 41st