Famciclovir Pharmacokinetics in Young Asian Elephants (Elephas maximus)
American Association of Zoo Veterinarians Conference 2003
Ramiro Isaza1, DVM, MS, DACZM; Robert P. Hunter2, MS, PhD; Laura K. Richman3,4, DVM, PhD, DACVP; Richard J. Montali3, DVM, DACZM, DACVP; Dennis L. Schmitt5, DVM, PhD, DACT; David E. Koch2; and William A. Lindsay6, DVM, DACVS
1Department of Clinical Sciences, Kansas State University, Manhattan, KS, USA; 2Zoological Pharmacology Laboratory, Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA; 3Smithsonian National Zoological Park, Washington, D.C., USA; 4Johns Hopkins School of Medicine, Baltimore, MD, USA; 5Southwest Missouri State University, Springfield, MO, USA; 6Ringling Bros. Center for Elephant Conservation, Polk City, FL, USA


Asian elephants (Elephas maximus) are susceptible to a unique infection caused by elephant endotheliotropic herpesvirus (EEHV).3,4 Worldwide, between the years 1983 and 2000, there have been 26 confirmed deaths from this virus in Asian elephants.2 Although most cases have been fatal, treatment with famciclovir (Famvir, SmithKline Beecham Pharmaceuticals, Philadelphia, PA, USA) has been associated with survival in three of six cases of EEHV infection proven by PCR.2,5,6 Dose selections for surviving elephants (5.5–8.0 mg/kg, PO every 8 h) were made without the benefit of elephant pharmacokinetics, and were a direct extrapolation from recommended human dosages (7 mg/kg, PO every 8 h).5,6 In this study, famciclovir was administered both orally and rectally in healthy young Asian elephants. The doses tested in this study were 5 mg/kg orally, 5 mg/kg rectally, and 15 mg/kg rectally. Blood samples were analyzed for famciclovir and penciclovir using a validated LC/MS assay. Famciclovir was absorbed well by both routes and underwent rapid biotransformation to the active compound penciclovir. None of the plasma samples had detectable famciclovir. Pharmacokinetic parameters for penciclovir were determined using noncompartmental analysis. After an oral dose of 5 mg/kg the Cmax was 1.3 µg/ml with a Tmax at 1.1 h. After a rectal dose of 5 mg/kg the Cmax was 1.2 µg/ml with a Tmax at 0.34 h. After a rectal dose of 15 mg the t½ was 2.6 h, with a Cmax of 3.6 µg/ml at Tmax 0.66 h. These results were similar to those reported in humans where an oral dose of 500 mg (7 mg/kg) had a t½ of about 2 h with a Cmax of 3.3 µg/ml.1 A dose range of 8–15 mg/kg given orally or rectally every 8 h should produce penciclovir concentrations in Asian elephants that are considered therapeutic in humans.

Literature Cited

1.  Hardman, J.G., L.E. Limbird and A.G. Gilman. 2001. In: Goodman and Gilman's The Pharmacological Basis of Therapeutics. Tenth edition. McGraw-Hill Co. New York, New York. USA. Pp. 1322–1324.

2.  Montali, R.J., Richman, L.K., Mikota, S.K., Schmitt, D.L., Larsen, R.S., Hildebrandt, T.B., Isaza, R., Lindsay, W.A. Management aspects of herpesvirus infections and tuberculosis in elephants. International Elephant and Rhino Research Symposium, Vienna, June 7–11, 2001.

3.  Richman, L.K., R.J. Montali, R.L. Garber, M.A. Kennedy, J. Lehnhardt, T. Hildebrandt, D. Schmitt, D. Hardy, D.J. Alcendor, G.S. Hayward. 1999a. Novel endotheliotropic herpesvirus fatal for Asian and African elephants. Science. 283:1171–1176.

4.  Richman, L.K., R.J. Montali, R.C. Cambre, D. Schmitt, D. Hardy, T. Hildebrandt, F.M. Hamzeh, A. Shahkolahi, G.S. Hayward. 2000. Clinical and pathological findings of a newly recognized disease of elephants caused by endotheliotropic herpesvirus. J. Wildl. Dis. 36:1–12.

5.  Schaftenaar, W., J.M.C.H. Mensink, A.M. de Boer, T.B. Hildebrandt, and J. Fickel. 2001. Successful treatment of a subadult Asian elephant bull (Elephas maximus) infected with the endotheliotropic elephant herpes virus. Verhber. Erkrg. Zootiere. P. 40.

6.  Schmitt, D., D.A. Hardy, R.J. Montali, LK Richman, Lindsay WA, R. Isaza, G. West. 2000. Use of famciclovir for the treatment of endotheliotropic herpesvirus infections in Asian elephants (Elephas maximus). J. Zoo Wildl. Med. 31:518–522.


Speaker Information
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Ramiro Isaza, DVM, MS, DACZM
Department of Clinical Sciences
Kansas State University
Manhattan, KS, USA

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