Vitreous penetration of orally administered famciclovir.
OBJECTIVE
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).


METHODS
Prospective interventional case series.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
W. K. Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA.
Deborah Y
DY
Chong
Mark W
MW
Johnson
Tony H
TH
Huynh
Edward F
EF
Hall
Grant M
GM
Comer
Douglas N
DN
Fish
D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D015828:Eye Infections, Viral / Q000188:drug therapy; D000077595:Famciclovir; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000493:pharmacokinetics*; D011446:Prospective Studies; D015882:Retinal Necrosis Syndrome, Acute / Q000188:drug therapy / Q000821:virology; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism*
D000998:Antiviral Agents; D011355:Prodrugs; D015075:2-Aminopurine; D000077595:Famciclovir