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J Ocul Pharmacol Ther. 1996 Summer;12(2):209-24.

Vitreous disposition of two acycloguanosine antivirals in the albino and pigmented rabbit models: a novel ocular microdialysis technique.

Author information

1
Department of Industrial and Physical Pharmacy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana, USA.

Abstract

A novel ocular microdialysis-perfusion technique was developed that allowed for the continuous sampling of the vitreous humor for drug. The technique produced accurate and rapid vitreous drug concentration time profiles with a resolution of 20 minutes on the time axis. The vitreous elimination of ganciclovir (GCV) and acyclovir (ACV) was extremely rapid, having vitreous half lives of 2.62 and 2.98 hours, respectively, and a transretinal mechanism of clearance was established for these compounds. Further, it was shown that the compounds do not exhibit saturation kinetics over the dosage ranges used in the clinical setting. Ocular pigmentation had a dramatic effect on the vitreous pharmacokinetics of GCV and ACV. The rate of elimination of GCV and ACV from the vitreous of the pigmented rabbit was much slower than the elimination from the albino rabbit (t 1/2 = 5.59 vs. 2.62 for GCV and 8.63 vs. 2.98 for ACV). The mean residence time of GCV was 2 times greater in the pigmented rabbit than in the albino rabbit and 3 times greater for ACV. Further, the volumes of distribution increased by 3.5 fold for GCV and 6.2 fold for ACV, respectively.

PMID:
8773936
DOI:
10.1089/jop.1996.12.209
[Indexed for MEDLINE]

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