Abstract
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
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