Intravitreal pharmacokinetics of plain and liposome-entrapped fluconazole in rabbit eyes.
The objective of our experiment was to study the pharmacokinetics of plain and liposome-encapsulated fluconazole after an intravitreal injection (100 microg/0.1 ml) in rabbit eyes. Equal concentrations of plain and liposome-entrapped fluconazole were injected intravitreally into albino rabbits through the pars plana after intravenous pentobarbitone anesthesia. The rabbits were sacrificed at various time intervals, and the concentration of fluconazole in vitreous, retina-choroid, aqueous humor and cornea was estimated using High Performance Liquid Chromatography (HPLC). Plain fluconazole showed a rapid vitreal clearance and a short half-life (3.08 hr), whereas liposome-entrapped fluconazole showed a longer half-life (23.40 hr). The terminal elimination constant (Ke) of the liposome-loaded drug from the vitreous was seven times less than the plain drug. In the plain fluconazole group, at 1 hr, a high concentration of the drug was found in the retina. To conclude, the elimination of fluconazole was primarily transretinal and was very rapid. Liposome encapsulation significantly increased the half-life of fluconazole in the vitreous cavity.
Gupta
S K
SK
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi. skgup@hotmail.com
Velpandian
T
T
Dhingra
N
N
Jaiswal
J
J
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002829:Choroid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D005260:Female; D015725:Fluconazole / Q000493:pharmacokinetics*; D006207:Half-Life; D008081:Liposomes / Q000493:pharmacokinetics*; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D012160:Retina / Q000378:metabolism; D014018:Tissue Distribution; D014822:Vitreous Body / Q000378:metabolism*
D000935:Antifungal Agents; D004337:Drug Carriers; D008081:Liposomes; D015725:Fluconazole