Vitreous penetration of Orally administered Valacyclovir

[Mike Bartolatz]

used to treat Ocular manifestations of the Herpes sx and zoster viruses

145, Issue 4, Pages 682-686 (April 2008)

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Vitreous Penetration of Orally Administered Valacyclovir

Tony H. Huynha, Mark W. Johnsona, Grant M. Comera, Douglas N. Fishb


Accepted 16 November 2007. published online 03 January 2008.

Purpose
To investigate the vitreous penetration of acyclovir, the active metabolite of valacyclovir, after oral administration of valacyclovir.

Design
Prospective, interventional case series.

Methods
Ten patients scheduled for elective pars plana vitrectomy at a single academic institution were given three oral doses of valacyclovir 1000 mg eight hours apart the day before surgery, with a fourth dose on the morning of surgery. Blood and undiluted vitreous samples were obtained during surgery and subsequently were analyzed with high-performance liquid chromatography to determine the concentrations of acyclovir present.

Results
Ten eyes of 10 subjects ranging in age from 46 to 83 years were included. All patients had normal renal and hepatic function as confirmed by metabolic panels obtained before surgery. Mean serum acyclovir concentration ± standard deviation was 4.41 ± 0.88 μg/ml (range, 3.18 to 5.92 μg/ml), mean vitreous acyclovir concentration was 1.03 ± 0.23 μg/ml (range, 0.67 to 1.33 μg/ml), and mean vitreous-to-serum concentration ratio of acyclovir was 0.24 ± 0.06 (range, 0.16 to 0.34).

Conclusions
Orally administered valacyclovir results in substantial vitreous penetration of acyclovir. The vitreous concentrations achieved in noninflamed eyes are within the reported inhibitory ranges for most strains of herpes simplex 1, herpes simplex 2, and varicella zoster virus. This suggests that orally administered valacyclovir may be an alternative to intravenous acyclovir in the treatment of acute retinal necrosis.

a W. K. Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan

b Department of Clinical Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado.

Inquiries to Mark W. Johnson, W. K. Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105

PII: S0002-9394(07)00986-5

doi:10.1016/j.ajo.2007