title: Estimates of the pharmacokinetics of famciclovir and its active metabolite penciclovir in young Asian elephants (Elephas maximus).
abstract: OBJECTIVE
  To determine plasma pharmacokinetics of penciclovir following oral and rectal administration of famciclovir to young Asian elephants (Elephas maximus).
  
  
  METHODS
  6 healthy Asian elephants (5 females and 1 male), 4.5 to 9 years old and weighing 1,646 to 2,438 kg.
  
  
  METHODS
  Famciclovir was administered orally or rectally in accordance with an incomplete crossover design. Three treatment groups, each comprising 4 elephants, received single doses of famciclovir (5 mg/kg, PO, or 5 or 15 mg/kg, rectally); there was a minimum 12-week washout period between subsequent famciclovir administrations. Serial blood samples were collected after each administration. Samples were analyzed for famciclovir and penciclovir with a validated liquid chromatography-mass spectroscopy assay.
  
  
  RESULTS
  Famciclovir was tolerated well for both routes of administration and underwent complete biotransformation to the active metabolite, penciclovir. Mean maximum plasma concentration of penciclovir was 1.3 μg/mL at 1.1 hours after oral administration of 5 mg/kg. Similar results were detected after rectal administration of 5 mg/kg. Mean maximum plasma concentration was 3.6 μg/mL at 0.66 hours after rectal administration of 15 mg/kg; this concentration was similar to results reported for humans receiving 7 mg/kg orally.
  
  
  CONCLUSIONS
  Juvenile Asian elephants are susceptible to elephant endotheliotropic herpesvirus. Although most infections are fatal, case reports indicate administration of famciclovir has been associated with survival of 3 elephants. In Asian elephants, a dose of 8 to 15 mg of famciclovir/kg given orally or rectally at least every 8 hours may result in penciclovir concentrations that are considered therapeutic in humans.
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA.
authors.forename: A Paige
authors.initials: AP
authors.lastname: Brock
authors.forename: Ramiro
authors.initials: R
authors.lastname: Isaza
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hunter
authors.forename: Laura K
authors.initials: LK
authors.lastname: Richman
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Montali
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Schmitt
authors.forename: David E
authors.initials: DE
authors.lastname: Koch
authors.forename: William A
authors.initials: WA
authors.lastname: Lindsay
mesh_terms: D015075:2-Aminopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004606:Elephants / Q000378:metabolism*; D000077595:Famciclovir; D005260:Female; D006147:Guanine; D006207:Half-Life; D008297:Male; D013058:Mass Spectrometry
chemical_list: D000998:Antiviral Agents; C053539:penciclovir; D015075:2-Aminopurine; D006147:Guanine; D000077595:Famciclovir; D000212:Acyclovir