Objective—To assess oral bioavailability (F) and pharmacokinetic
characteristics of the R- and S-enantiomers
of ketoprofen administered IV and orally to
captive Asian elephants (Elephas maximus).
Animals—5 adult Asian elephants.
Procedure—Elephants received single treatments of
racemic ketoprofen at a dose of 2.2 mg/kg, administered
IV and orally, in a complete crossover design.
Blood samples were collected at intervals during the
24 hours following treatment. At least 4 weeks
elapsed between drug administrations. Samples
were analyzed for R- and S-ketoprofen with a validated
liquid chromatography-mass spectroscopic assay.
Pharmacokinetic parameters were determined by use
of noncompartmental analysis.
Results—The enantiomers of ketoprofen were
absorbed well after oral administration, with median F
of 101% for R-ketoprofen and 85% for S-ketoprofen.
Harmonic mean half-life ranged from 3.8 to 5.5 hours,
depending on route of administration and enantiomer.
The area under the concentration-time curve, mean
residence time, apparent volume of distribution, plasma
clearance, and maximum plasma concentration
values were all significantly different between the 2
enantiomers for both routes of administration.
Conclusion and Clinical Relevance—Ketoprofen
has a long terminal half-life and complete absorption
in this species. Based on the pharmacokinetic data, a
dosage of ketoprofen of 1 mg/kg every 48 hours to 2
mg/kg every 24 hours, PO or IV, is recommended for
use in Asian elephants, although the safety and efficacy
of ketoprofen during long-term administration in
elephants have not been determined. (Am J Vet Res
Objective—To evaluate the humoral immune response of Asian elephants to a primary IM vaccination with either 1 or 2 doses of a commercially available inactivated rabies virus vaccine and evaluate the anamnestic response to a 1-dose booster vaccination.
Animals—16 captive Asian elephants.
Procedures—Elephants with no known prior rabies vaccinations were assigned into 2 treatment groups of 8 elephants; 1 group received 1 dose of vaccine, and the other group received 2 doses of vaccine 9 days apart. All elephants received one or two 4-mL IM injections of a monovalent inactivated rabies virus vaccine. Blood was collected prior to vaccination (day 0) and on days 9, 35, 112, and 344. All elephants received 1 booster dose of vaccine on day 344, and a final blood sample was taken 40 days later (day 384). Serum was tested for rabies virus–neutralizing antibodies by use of the rapid fluorescent focus inhibition test.
Results—All elephants were seronegative prior to vaccination. There were significant differences in the rabies geometric mean titers between the 2 elephant groups at days 35, 112, and 202. Both groups had a strong anamnestic response 40 days after the booster given at day 344.
Conclusions and Clinical Relevance—Results confirmed the ability of Asian elephants to develop a humoral immune response after vaccination with a commercially available monovalent inactivated rabies virus vaccine and the feasibility of instituting a rabies virus vaccination program for elephants that are in frequent contact with humans. A 2-dose series of rabies virus vaccine should provide an adequate antibody response in elephants, and annual boosters should maintain the antibody response in this species.
Objective—To determine the pharmacokinetics of
enrofloxacin after oral administration to captive elephants.
Animals—6 clinically normal adult Asian elephants
Procedure—Each elephant received a single dose of
enrofloxacin (2.5 mg/kg, PO). Three elephants
received their complete diet (pellets and grain) within
2 hours after enrofloxacin administration, whereas
the other 3 elephants received only hay within 6
hours after enrofloxacin administration. Serum concentrations
of enrofloxacin and ciprofloxacin were
measured by use of high-performance liquid
Results—Harmonic mean half-life after oral administration
was 18.4 hours for all elephants. Mean ± SD peak
serum concentration of enrofloxacin was 1.31 ±
0.40 µg/mL at 5.0 ± 4.2 hours after administration. Mean
area under the curve was 20.72 ± 4.25 (µg × h)/mL.
Conclusions and Clinical Relevance—Oral administration
of enrofloxacin to Asian elephants has a prolonged
elimination half-life, compared with the elimination
half-life for adult horses. In addition, potentially
therapeutic concentrations in elephants were
obtained when enrofloxacin was administered orally at
a dosage of 2.5 mg/kg. Analysis of these results suggests
that enrofloxacin administered with feed in the
manner described in this study could be a potentially
useful antimicrobial for use in treatment of captive
Asian elephants with infections attributable to organisms,
such as Bordetella spp, Escherichia coli,
Mycoplasma spp, Pasteurella spp, Haemophilus spp,
Salmonella spp, and Staphylococcus spp. (Am J Vet
Objective—To determine pharmacokinetics and tissue
concentrations of azithromycin in ball pythons
( Python regius ) after IV or oral administration of a single
Animals—2 male and 5 female ball pythons.
Procedures—Using a crossover design, each snake
was given a single dose of azithromycin (10 mg/kg) IV.
After a 4-week washout period, each snake was given
a single dose of azithromycin (10 mg/kg) orally. Blood
samples were collected prior to dose administration
and 1, 3, 6, 12, 24, 48, 72, and 96 hours after
azithromycin administration. Azithromycin was quantitated
by use of liquid chromatography-mass spectrometry.
Results—After IV administration, azithromycin had an
apparent volume of distribution of 5.69 L/kg and a
plasma clearance of 0.19 L/h/kg. Harmonic means for
the terminal half-life were 17 hours following IV
administration and 51 hours following oral administration.
Mean residence times were 37 and 94 hours following
IV and oral administration, respectively.
Following oral administration, azithromycin had a peak
plasma concentration (Cmax) of 1.04 µg/mL, a time to
Cmax of 8.4 hours, and a prolonged mean absorption
time of 57 hours. Mean oral bioavailability was 77%.
Tissue concentrations ranged from 4 to 140 times the
corresponding plasma concentration at 24 and 72
hours after azithromycin administration.
Conclusions and Clinical Relevance—Azithromycin
is well absorbed and tolerated by ball pythons. On the
basis of plasma pharmacokinetics and tissue concentration
data, we suggest an azithromycin dosage in
ball pythons of 10 mg/kg, orally, every 2 to 7 days,
depending upon the site of infection and susceptibil
ity of the infective organism. (Am J Vet Res 2003;64:225–228)
Objective—To determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws.
Animals—10 healthy blue and gold macaws.
Procedures—In a crossover study, marbofloxacin (2.5 mg/kg) was administered orally (via crop gavage) to 5 birds and IV to 5 birds. Blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after marbofloxacin administration. After a 4-week washout period, the study was repeated, with the first 5 birds receiving the dose IV and the second 5 birds receiving the dose orally. Serum marbofloxacin concentrations were quantitated by use of a validated liquid chromatography–mass spectrometry assay.
Results—After oral administration, mean ± SD area under the curve was 7.94 ± 2.08 μg•h/mL, maximum plasma concentration was 1.08 ± 0.316 μg/mL, and bioavailability was 90.0 ± 31%. After IV administration of marbofloxacin, the apparent volume of distribution was 1.3 ± 0.32 L/kg, plasma clearance was 0.29 ± 0.078 L/h/kg, area under the curve was 9.41 ± 2.84 μg•h/mL, and the harmonic mean terminal half-life was 4.3 hours.
Conclusions and Clinical Relevance—Single IV and orally administered doses of marbofloxacin were well tolerated by blue and gold macaws. The orally administered dose was well absorbed. Administration of marbofloxacin at a dosage of 2.5 mg/kg, PO, every 24 hours may be appropriate to control bacterial infections susceptible to marbofloxacin in this species.
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.