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 describe the pharmacokinetics of
cyclosporine (CyA) in healthy dogs after oral administration
alone or in combination with orally administered
Animals—10 healthy adult Beagles.
Procedure—Dogs were randomly assigned to
receive CyA alone or CyA in combination with cimetidine.
After a washout period of 2 weeks, dogs then
received the alternate treatment. The CyA plus cimetidine
treatment required administration of cimetidine
(15 mg/kg of body weight, PO, q 8 h) for 8 days and
administration of CyA (5 mg/kg, PO, q 24 h) on days
6 through 8. The CyA treatment alone required
administration of CyA (5 mg/kg, PO, q 24 h) for 3
days. On the third day of CyA administration during
each treatment, blood samples were collected immediately
before (time 0) and 0.5, 1, 1.5, 2, 2.5, 3, 5, 7,
9, 11, 13, 15, 21, and 24 hours after initiating CyA
Results—Time until maximum CyA concentration
was significantly longer for CyA in combination with
cimetidine. Assessment of estimated pharmacokinetic
variables revealed a significantly faster rate of
change in the distribution phase for CyA in combination
with cimetidine. Maximum CyA concentration
differed significantly among dogs but did not differ
significantly between treatments.
Conclusions and Clinical Relevance—Analysis of
our data suggests that cimetidine may affect absorption
of orally administered CyA, but overall, it does
not affect the pharmacokinetics of CyA. There is considerable
variability in the maximum concentration of
CyA among dogs, and monitoring of blood concentrations
of CyA during treatment is advised. (Am J Vet
Objective—To determine the pharmacokinetics of marbofloxacin after oral administration every 24 hours to rabbits during a 10-day period.
Animals—8 healthy 9-month-old female New Zealand White rabbits.
Procedures—Marbofloxacin (5 mg/kg) was administered orally every 24 hours to 8 rabbits for 10 days. The first day of administration was designated as day 1. Blood samples were obtained at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours on days 1 and 10 of marbofloxacin administration. Plasma marbofloxacin concentrations were quantitated by use of a validated liquid chromatography–mass spectrometry assay. Pharmacokinetic analysis of marbofloxacin was analyzed via noncompartmental methods.
Results—After oral administration, mean ± SD area under the curve was 10.50 ± 2.00 μg·h/mL and 10.90 ± 2.45 μg·h/mL, maximum plasma concentration was 1.73 ± 0.35 μg/mL and 2.56 ± 0.71 μg/mL, and harmonic mean terminal half-life was 8.0 hours and 3.9 hours for days 0 and 10, respectively.
Conclusions and Clinical Relevance—Marbofloxacin administered orally every 24 hours for 10 days appeared to be absorbed well and tolerated by rabbits. Administration of marbofloxacin at a dosage of 5 mg/kg, PO, every 24 hours is recommended for rabbits to control infections attributable to susceptible bacteria.
Objective—To determine the plasma pharmacokinetics
and synovial fluid concentrations after oral administration
of single and multiple doses of celecoxib in
Animals—7 adult Greyhounds.
Procedure—Dogs received celecoxib (median
dose, 11.8 mg/kg [range, 11.5 to 13.6 mg/kg], PO,
q 24 h) for 10 days. Blood samples were collected
prior to administration of celecoxib and serially for
24 hours after the 1st and 10th doses were administered.
A synovial joint catheter was placed into a
stifle joint in each dog for collection of synovial fluid
samples. Concentrations of celecoxib in plasma and
synovial fluid were quantified by use of a validated
liquid chromatography/mass spectrometry method.
Identification of hydroxy- and carboxyl-celecoxib in
plasma and synovial fluid was also performed.
Pharmacokinetic parameters were determined by
use of noncompartmental analysis.
Results—Administration of multiple doses of celecoxib
resulted in a significant decrease (40%) in median
area under the curve (AUC) values and a corresponding
decrease in median maximum concentrations
(Cmax; 2,620 to 2,032 ng/mL) between the 1st
and 10th doses. Synovial fluid concentrations were
less than the corresponding plasma concentrations at
all times except 24 hours after administration of the
10th dose of celecoxib.
Conclusions and Clinical Relevance—Celecoxib distributes
into the synovial fluid of Greyhounds.
Although the exact mechanism for the decreases in
AUC and Cmax is not known, results suggested that
the plasma pharmacokinetics of celecoxib are different
after administration of multiple doses in
Greyhounds. These findings warrant further investigation
on the absorption, distribution, metabolism, and
elimination of celecoxib in Greyhounds and other
breeds of dogs. (Am J Vet Res 2005;66:1441–1445)
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.