Feline herpesvirus-1 is a major cause of respiratory and ocular disease in cats, with an estimated seroprevalence in feline populations of 50% to 97%.1-3 Infection of susceptible kittens with FHV-1 typically causes moderate to severe upper respiratory tract and ocular disease with approximately 100% morbidity.4 Illness may be fatal, especially in young kittens. Following primary exposure, FHV-1 establishes lifelong neural latency in at least 80% of cats, and periods of viral reactivation occur throughout life in many of these cats.5 Herpetic infection may be associated with conjunctivitis,6 rhinosinusitis,7 keratitis,8 corneal sequestration,9 eosinophilic keratitis,9 anterior uveitis,10 or dermatitis.11,12 As such, primary and recrudescent herpetic disease in cats represents a diverse array of common and often frustrating clinical syndromes worldwide.
Presently, in the United States, there are no antiviral drugs approved for treatment of cats infected with FHV-1. However, several antiviral agents developed for treatment of humans infected with herpesviruses have been used in cats.13,14 Unfortunately, many of the agents developed for humans infected with herpesviruses have low efficacy against FHV-1,15,16 are poorly bioavailable in cats,17 or are toxic when systemically administered to cats.17,18 Toxicity is of less concern when antiviral agents developed for the treatment of herpesviruses in humans are applied topically to cats' eyes; however, concerns regarding their efficacy against FHV-1 remain.15,16 Therefore, development or discovery of a safe and effective antiviral agent for treating cats infected with FHV-1 is an important goal.
Anecdotal reports of the use of famciclovir at approximately 6 to 10 mg/kg every 24 or 12 hours to treat cats with herpetic disease have recently emerged. Famciclovir is a prodrug of the antiviral drug penciclovir. Penciclovir is a nucleoside deoxyguanosine analogue with a similar mechanism of action as acyclovir and potent antiviral activity for the human herpesviruses varicella zoster virus and herpes simplex virus types 1 and 2.19 Recently, we examined the antiviral efficacy of penciclovir and other antiviral drugs against FHV-1 cultured in vitro.16 The median penciclovir concentration at which FHV-1 plaque numbers were reduced by 50% relative to control wells (13.9μM [3,500 ng/mL]) was similar to other drugs that have had some clinical effect as topical treatments for cats infected with FHV-1 and was superior to that reported for acyclovir, the only drug sometimes recommended for systemic administration to FHV-1–infected cats.15,16 However, to the authors' knowledge, the pharmacokinetics and safety of penciclovir following oral administration of famciclovir to cats have not been determined. Therefore, the purpose of the study reported here was to investigate the pharmacokinetics and safety of penciclovir following single and multiple oral doses of famciclovir in healthy cats.
Maximum detected plasma penciclovir concentration
Time after oral administration at which Cmax was detected
Elimination rate constant
Area under the plasma penciclovir concentration-time curve
Apparent elimination half-life
Mean plasma penciclovir concentration during the dosing interval at steady state
Minimum detected plasma penciclovir concentration during the dosing interval at steady state
Area under the plasma penciclovir concentration-time curve during the dosing interval
Area under the plasma penciclovir concentration-time curve extrapolated to infinity
Whiskas Dry Kitten Food, Waltham USA Inc, Vernon, Calif.
Famvir (125-mg, round, film-coated biconvex tablet with beveled edges), Novartis Pharmaceuticals Corp, East Hanover, NJ.
Waltham Coat Care Tuna Formula, Waltham USA Inc, Vernon, Calif.
Arrow International Inc, Reading, Pa.
Calbiochem, La Jolla, Calif.
Sigma Aldrich, St Louis, Mo.
Glas-Col Apparatus Co, Terre Haute, Ind.
LTQ, Thermo Electron Corp, San Jose, Calif.
Model 1100, Agilent Technologies, Palo Alto, Calif.
Zorbax XDB-phenyl 3-μm × 150-mm column, MacMod Analytical Inc, Chads Ford, Pa.
WinNonlin, version 5.0.1, Pharsight Corp, Palo Alto, Calif.
SigmaPlot, version 9.01, Systat Software Inc, Point Richmond, Calif.
IDEXX Reference Laboratories, West Sacramento, Calif.
Studdert MJ, Martin MC. Virus diseases of the respiratory tract of cats. 1. Isolation of feline rhinotracheitis virus. Aust Vet J 1970;46:99–104.
Maggs DJ, Lappin MR, Reif JS, et al. Evaluation of serologic and viral detection methods for diagnosing feline herpesvirus-1 infection in cats with acute respiratory tract or chronic ocular disease. J Am Vet Med Assoc 1999;214:502–507.
Hoover EA, Rohovsky MW, Griesemer RA. Experimental feline viral rhinotracheitis in the germfree cat. Am J Pathol 1970;58:269–282.
Gaskell RM, Povey RC. Experimental induction of feline viral rhinotracheitis virus re-excretion in FVR-recovered cats. Vet Rec 1977;100:128–133.
Nasisse MP, Guy JS, Stevens JB, et al. Clinical and laboratory findings in chronic conjunctivitis in cats: 91 cases (1983–1991). J Am Vet Med Assoc 1993;203:834–837.
Johnson LR, Foley JE, De Cock HE, et al. Assessment of infectious organisms associated with chronic rhinosinusitis in cats. J Am Vet Med Assoc 2005;227:579–585.
Nasisse MP, English RV, Tompkins MB, et al. Immunologic, histologic, and virologic features of herpesvirus-induced stromal keratitis in cats. Am J Vet Res 1995;56:51–55.
Nasisse MP, Glover TL, Moore CP, et al. Detection of feline herpesvirus 1 DNA in corneas of cats with eosinophilic keratitis or corneal sequestration. Am J Vet Res 1998;59:856–858.
Maggs DJ, Lappin MR, Nasisse MP. Detection of feline herpesvirus-specific antibodies and DNA in aqueous humor from cats with or without uveitis. Am J Vet Res 1999;60:932–936.
Holland JL, Outerbridge CA, Affolter VK, et al. Detection of feline herpesvirus 1 DNA in skin biopsy specimens from cats with or without dermatitis. J Am Vet Med Assoc 2006;229:1442–1446.
Hargis AM, Ginn PE, Mansell JE, et al. Ulcerative facial and nasal dermatitis and stomatitis in cats associated with feline herpesvirus 1. Vet Dermatol 1999;10:267–274.
Stiles J. Treatment of cats with ocular disease attributable to herpesvirus infection: 17 cases (1983–1993). J Am Vet Med Assoc 1995;207:599–603.
Nasisse MP, Guy JS, Davidson MG, et al. In vitro susceptibility of feline herpesvirus-1 to vidarabine, idoxuridine, trifluridine, acyclovir, or bromovinyldeoxyuridine. Am J Vet Res 1989;50:158–160.
Maggs DJ, Clarke HE. In vitro efficacy of ganciclovir, cidofovir, penciclovir, foscarnet, idoxuridine, and acyclovir against feline herpesvirus type-1. Am J Vet Res 2004;65:399–403.
Nasisse MP, Dorman DC, Jamison KC, et al. Effects of valacyclovir in cats infected with feline herpesvirus 1. Am J Vet Res 1997;58:1141–1144.
Filer CW, Ramji JV, Allen GD, et al. Metabolic and pharmacokinetic studies following oral administration of famciclovir to the rat and dog. Xenobiotica 1995;25:477–490.
Gibaldi M, Perrier D. Noncompartmental analysis based on statistical moment theory. In: Gibaldi M, Perrier D, eds. Pharmaco-kinetics. 2nd ed. New York: Marcel Dekker Inc, 1982;409–418.
Pue MA, Pratt SK, Fairless AJ, et al. Linear pharmacokinetics of penciclovir following administration of single oral doses of famciclovir 125, 250, 500 and 750 mg to healthy volunteers. J Antimicrob Chemother 1994;33:119–127.
Clarke SE, Harrell AW, Chenery RJ. Role of aldehyde oxidase in the in vitro conversion of famciclovir to penciclovir in human liver. Drug Metab Dispos 1995;23:251–254.
Dick RA, Kanne DB, Casida JE. Identification of aldehyde oxidase as the neonicotinoid nitroreductase. Chem Res Toxicol 2005;18:317–323.