Vitreous Penetration of Orally Administered Valacyclovir

• Published in: American journal of ophthalmology Vol. 145; no. 4; pp. 682 - 686
• Main Authors: Huynh, Tony H, Johnson, Mark W, Comer, Grant M, Fish, Douglas N
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-04-2008; Elsevier; Elsevier Limited
• Subjects: Acyclovir - analogs & derivatives; Acyclovir - blood; Acyclovir - pharmacokinetics; Administration, Oral; Aged; Aged, 80 and over; Antiviral Agents - pharmacokinetics; Biological and medical sciences; Chromatography; Chromatography, High Pressure Liquid; Colleges & universities; Drug dosages; Drug therapy; Female; Herpes viruses; Humans; Male; Medical sciences; Middle Aged; Miscellaneous; Ophthalmology; Patients; Prodrugs - pharmacokinetics; Prospective Studies; Standard deviation; Surgery; Valine - analogs & derivatives; Valine - pharmacokinetics; Vitrectomy; Vitreous Body - metabolism; Acyclic nucleoside; Purine nucleoside; Oral administration; Valaciclovir; Nucleoside analog; Antiviral; Vitreous body; Ophthalmology; Prodrug; DNA polymerase inhibitor
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/j.ajo.2007.11.016

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.