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  • Author or Editor: John A. Griffioen x
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Abstract

OBJECTIVE

To evaluate the pharmacokinetics of famciclovir and its metabolite penciclovir following a single dose administered orally and rectally in African elephants (Loxodonta africana).

ANIMALS

15 African elephants (6 males and 9 females) of various ages.

METHODS

Famciclovir (15 mg/kg) was administered orally or per rectum once, with at least a three-week washout period between administrations. Blood was collected at 13 different timepoints per administration for 6 elephants, occurring between February and March 2020. An additional 9 elephants were sampled at variable timepoints per administration utilizing a sparse sampling design between July 2020 and January 2021. Plasma famciclovir and penciclovir levels were measured via HPLC and fluorescence detection. Pharmacokinetic analysis was completed in the summer of 2021 using noncompartmental analysis and nonlinear mixed-effects modeling.

RESULTS

Famciclovir was not detected in any sample, suggesting complete metabolism. Key pharmacokinetic parameters for penciclovir following oral administration were time to maximum concentration (tmax; 2.12 hours), area under the concentration-versus-time curve (AUC; 33.93 μg·h/mL), maximum observed concentration (Cmax; 3.73 μg/mL), and absorption half-life (t1/2; 0.65 hours). Following rectal administration, the values were: tmax, 0.65 hours; AUC, 15.62 μg·h/mL; Cmax, 2.52 μg/mL; and absorption t1/2, 0.13 hours.

CONCLUSIONS

Famciclovir was rapidly metabolized to penciclovir. Oral administration resulted in slower absorption but higher maximum plasma concentration and higher AUC compared to rectal administration.

CLINICAL RELEVANCE

African elephants administered famciclovir via oral and rectal routes resulted in measurable serum penciclovir, and these findings may be utilized by clinicians treating viral infections in this species.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine (1) if chemokine (C-X-C motif) ligand 1 (CXCL1), matrix metalloproteinase 8 (MMP8), interleukin-10 (IL-10), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) can be detected in serum from Asian elephants, and (2) if their concentrations are significantly elevated in Mycobacterium tuberculosis (M.tb) culture–positive elephants compared to –negative elephants. CXCL1, MMP8, IL-10, IFN-γ, and TNF-α were recently identified as potential diagnostic biomarkers for pulmonary tuberculosis in experimental studies in animals and humans. Therefore, we hypothesized that they would be detectable and significantly elevated in M.tb culture–positive elephants compared to M.tb culture–negative elephants.

SAMPLE

101 Asian elephant serum samples, including 91 samples from 6 M.tb-negative elephants and 10 samples from 5 M.tb-positive elephants (none of which exhibited clinical signs of disease). M.tb status was determined by trunk wash culture.

PROCEDURES

Commercially available ELISA kits were used to determine the concentrations of each biomarker in serum samples.

RESULTS

Biomarker concentrations were below the limit of detection for the assay in 100/101 (99%) samples for CXCL1, 98/101 (97%) samples for MMP8, 85/101 (84%) samples for IL-10, 75/101 (74%) samples for IFN-γ, and 45/101 (45%) samples for TNF-α. Multiple M.tb culture–positive elephants did not have detectable levels of any of the 5 biomarkers.

CLINICAL RELEVANCE

CXCL1, MMP8, IL-10, IFN-γ, and TNF-α were not elevated in M.tb culture–positive Asian elephants compared to M.tb culture–negative Asian elephants. This may be related to disease state (ie, clinically asymptomatic). More sensitive assays are needed to better understand the role of these biomarkers in M.tb infection in Asian elephants.

Open access
in American Journal of Veterinary Research