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).

ANIMALS:

6 healthy Asian elephants (5 females and 1 male), 4.5 to 9 years old and weighing 1,646 to 2,438 kg.

PROCEDURES:

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 AND CLINICAL RELEVANCE:

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: A Paige Brock, Ramiro Isaza, Robert P Hunter, Laura K Richman, Richard J Montali, Dennis L Schmitt, David E Koch, William A Lindsay
• Journal: American journal of veterinary research (Am J Vet Res) Vol. 73 Issue 12 Pg. 1996-2000 (Dec 2012) ISSN: 1943-5681 [Electronic] United States
• PMID: 23176429 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• penciclovir
• 2-Aminopurine
• Guanine
• Famciclovir
• Acyclovir

Topics

• 2-Aminopurine (administration & dosage, analogs & derivatives, blood, pharmacokinetics)
• Acyclovir (administration & dosage, analogs & derivatives, blood, pharmacokinetics)
• Administration, Oral
• Administration, Rectal
• Animals
• Antiviral Agents (administration & dosage, blood, pharmacokinetics)
• Area Under Curve
• Chromatography, Liquid
• Cross-Over Studies
• Elephants (metabolism)
• Famciclovir
• Female
• Guanine
• Half-Life
• Male
• Mass Spectrometry