title: Pharmacokinetics of famciclovir and penciclovir in tears following oral administration of famciclovir to cats: a pilot study.
abstract: OBJECTIVE
  To validate a means of collecting tears from cats, develop an assay for quantifying famciclovir and penciclovir in tears, and to assess famciclovir and penciclovir concentrations and pharmacokinetics in the tears of cats being treated orally with famciclovir for suspected herpetic disease.
  
  
  METHODS
  Seven client-owned cats.
  
  
  METHODS
  Cats were treated orally with a median (range) dose of 40 (39-72) mg of famciclovir/kg three times daily for at least 24 h. At various time points following famciclovir administration, tear samples were collected using Schirmer tear test strips. Tear famciclovir and penciclovir concentrations were measured using liquid chromatography-mass spectrometry, and concentration-time profiles were analyzed noncompartmentally. The relationship between famciclovir dose and tear penciclovir concentration near its maximum was evaluated using least squares linear regression.
  
  
  RESULTS
  Maximum tear famciclovir concentration of 0.305 μg/mL occurred at 2.64 h; elimination half-life was 2.28 h. Maximum tear penciclovir concentration (0.981 μg/mL) occurred 2.25 h following oral administration of famciclovir; elimination half-life was 2.77 h. A significant positive correlation was noted between famciclovir dose and tear penciclovir concentration at various time points between 0.5 and 3.75 h following drug administration (P = 0.025). Tear penciclovir concentration exceeded the concentration shown to have in vitro efficacy against feline herpesvirus (FHV-1) (0.304 μg/mL) in about half of samples collected.
  
  
  CONCLUSIONS
  Oral administration of 40 mg of famciclovir/kg to cats resulted in a tear penciclovir concentration-time profile that approximated the plasma penciclovir concentration-time profile and frequently achieved a penciclovir concentration at the ocular surface likely to be effective against FHV-1.
authors.affiliation: Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Thomasy
authors.forename: Jill C
authors.initials: JC
authors.lastname: Covert
authors.forename: Scott D
authors.initials: SD
authors.lastname: Stanley
authors.forename: David J
authors.initials: DJ
authors.lastname: Maggs
mesh_terms: D015075:2-Aminopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D000212:Acyclovir / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005128:Eye Diseases / Q000188:drug therapy / Q000662:veterinary* / Q000821:virology; D000077595:Famciclovir; D006147:Guanine; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000662:veterinary*; D010865:Pilot Projects; D013048:Specimen Handling / Q000379:methods / Q000662:veterinary; D013666:Tears / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; C053539:penciclovir; D015075:2-Aminopurine; D006147:Guanine; D000077595:Famciclovir; D000212:Acyclovir