Vitreous Penetration of Orally Administered Famciclovir

Abstract

To determine the vitreous penetration of penciclovir (Denavir; GlaxoSmithKline, Philadelphia, Pennsylvania, USA) after oral administration of the prodrug famciclovir (Famvir; Novartis Pharmaceuticals Corp, East Hanover, New Jersey, USA). Prospective interventional case series. Ten patients undergoing elective pars plana vitrectomy at a single institution were enrolled to take 3 oral doses of famciclovir 500 mg the day preceding surgery and a fourth dose on the morning of surgery. Blood and undiluted vitreous samples were acquired from each patient during surgery. High-performance liquid chromatography was used to determine the concentration of penciclovir in each sample. Exclusion criteria included prior vitrectomy, compromised blood-retina barrier, renal or hepatic disease, human immunodeficiency virus infection, bone marrow or renal transplantation, pregnancy or breastfeeding, history of adverse reaction or allergy to famciclovir or penciclovir, and antiviral, probenecid, or cimetidine use within 1 month of surgery. Ten eyes of 10 patients ranging in age from 26 to 82 were included. All patients had normal renal and hepatic function as determined by history and laboratory values. Mean serum penciclovir concentration +/- standard deviation was 4.45 +/- 1.31 microg/ml (range, 2.51 to 6.34 microg/ml). Mean vitreous penciclovir concentration was 1.21 +/- 0.38 microg/ml (range, 0.39 to 1.88 microg/ml). Mean vitreous-to-serum concentration ratio of penciclovir was 0.28 +/- 0.09 (range, 0.16 to 0.41). Oral administration of famciclovir results in vitreous concentrations of penciclovir within the inhibitory ranges for herpes simplex 1, herpes simplex 2, and varicella zoster virus. Oral famciclovir may be a reasonable alternative to intravenous acyclovir (Zovirax; GlaxoSmithKline) in the treatment of acute retinal necrosis, especially in cases of acyclovir resistance or patient inability to tolerate prolonged intravenous treatment.