Objective—To compare serum disposition of sulfamethoxazole
and trimethoprim after IV administration
to donkeys, mules, and horses.
Animals—5 donkeys, 5 mules, and 3 horses.
Procedure—Blood samples were collected before
(time 0) and 5, 15, 30, and 45 minutes and 1, 1.25, 1.5,
1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 24 hours
after IV administration of sulfamethoxazole
(12.5 mg/kg) and trimethoprim (2.5 mg/kg). Serum
was analyzed in triplicate with high-performance liquid
chromatography for determination of sulfamethoxazole
and trimethoprim concentrations.
Serum concentration-time curve for each animal was
analyzed separately to estimate noncompartmental
Results—Clearance of trimethoprim and sulfamethoxazole
in donkeys was significantly faster
than in mules or horses. In donkeys, mean residence
time (MRT) of sulfamethoxazole (2.5 hours) was less
than half the MRT in mules (6.2 hours); MRT of
trimethoprim in donkeys (0.8 hours) was half that in
horses (1.5 hours). Volume of distribution at steady
state (Vdss) for sulfamethoxazole did not differ, but
Vdss of trimethoprim was significantly greater in horses
than mules or donkeys. Area under the curve for
sulfamethoxazole and trimethoprim was higher in
mules than in horses or donkeys.
Conclusions and Clinical Relevance—Dosing intervals
for IV administration of trimethoprim-sulfamethoxazole
in horses may not be appropriate for
use in donkeys or mules. Donkeys eliminate the
drugs rapidly, compared with horses. Ratios of
trimethoprim and sulfamethoxazole optimum for
antibacterial activity are maintained for only a short
duration in horses, donkeys, and mules. (Am J Vet Res
Objective—To describe the pharmacokinetics of
phenylbutazone and oxyphenbutazone after IV administration
in miniature donkeys.
Animals—6 clinically normal miniature donkeys.
Procedure—Blood samples were collected before
and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360,
and 480 minutes after IV administration of phenylbutazone
(4.4 mg/kg of body weight). Serum was analyzed
in triplicate by use of high-performance liquid
chromatography for determination of phenylbutazone
and oxyphenbutazone concentrations. The serum
concentration-time curve for each donkey was analyzed
separately to estimate model-independent pharmacokinetic
Results—Serum concentrations decreased rapidly
after IV administration of phenylbutazone, and they
reached undetectable concentrations within 4 hours.
Values for mean residence time ranged from 0.5 to
3.0 hours (median, 1.1 hour), whereas total body
clearance ranged from 4.2 to 7.5 ml/kg/ min (mean,
5.8 ml/kg/ min). Oxyphenbutazone appeared rapidly in
the serum; time to peak concentration ranged from
13 to 41 minutes (mean, 26.4 minutes), and peak concentration
in serum ranged from 2.8 to 4.0 mg/ml
(mean, 3.5 μg/ml).
Conclusion and Clinical Relevance—Clearance of
phenylbutazone in miniature donkeys after injection of
a single dose (4.4 mg/kg, IV) is rapid. Compared with
horses, miniature donkeys may require more frequent
administration of phenylbutazone to achieve therapeutic
efficacy. (Am J Vet Res 2001;62:673–675)
Objective—To validate use of high-performance liquid
chromatography (HPLC) in determining
imipramine concentrations in equine serum and to
determine pharmacokinetics of imipramine in narcoleptic
Animals—5 horses with adult-onset narcolepsy.
Procedure—Blood samples were collected before
(time 0) and 3, 5, 10, 15, 20, 30, and 45 minutes and
1, 2, 3, 4, 6, 8, 12, and 24 hours after IV administration
of imipramine hydrochloride (2 or 4 mg/kg of body
weight). Serum was analyzed, using HPLC, to determine
imipramine concentration. The serum concentration-versus-time curve for each horse was analyzed
separately to estimate pharmacokinetic values.
Results—Adverse effects (muscle fasciculations,
tachycardia, hyperresponsiveness to sound, and
hemolysis) were detected in most horses when
serum imipramine concentrations were high, and
these effects were most severe in horses receiving 4
mg of imipramine/kg. Residual adverse effects were
not apparent. Value (mean ± SD) for area under the
curve was 3.9 ± 0.7 h × μg/ml, whereas volume of
distribution was 584 ± 161.7 ml/kg, total body clearance
was 522 ± 102 ml/kg/h, and mean residence
time was 1.8 ± 0.6 hours. One horse had signs of narcolepsy
6 and 12 hours after imipramine administration;
corrresponding serum imipramine concentrations
were less than the therapeutic range.
Conclusions and Clinical Relevance—Potentially
serious adverse effects may be seen in horses administered
doses of imipramine that exceed a dosage of
2 mg/kg. Total body clearance of imipramine in horses
is slower than that in humans; thus, the interval
between subsequent doses should be longer in horses.
(Am J Vet Res 2001;62:783–786)
Objective—To compare plasma disposition of the
R(–) and S(+) enantiomers of carprofen after IV administration
of a bolus dose to donkeys and horses.
Animals—5 clinically normal donkeys and 3 clinically
Procedure—Blood samples were collected from all
animals at time 0 (before) and at 10, 15, 20, 30, and
45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24,
28, 32, and 48 hours after IV administration of a
bolus of carprofen (0.7 mg/kg). Plasma was analyzed
in triplicate via high-performance liquid chromatography
to determine the concentrations of the
carprofen enantiomers. A plasma concentration-time
curve for each donkey and horse was analyzed
separately to estimate noncompartmental pharmacokinetic
Results—In donkeys and horses, the area under the
plasma concentration versus time curve (AUC) was
greater for the R(–) carprofen enantiomer than it was
for the S(+) carprofen enantiomer. For the R(–) carprofen
enantiomer, the AUC and mean residence time
(MRT) were significantly less and total body clearance
(ClT) was significantly greater in horses, compared
with donkeys. For the S(+) carprofen enantiomer,
AUC and MRT were significantly less and ClT and
apparent volume of distribution at steady state were
significantly greater in horses, compared with donkeys.
Conclusions and Clinical Relevance—Results have
suggested that the dosing intervals for carprofen that
are used in horses may not be appropriate for use in
donkeys. (Am J Vet Res 2004;65:1479–1482)
Objective—To determine plasma disposition after
dermal application of a liposome-encapsulated formulation
of lidocaine in cats.
Animals—6 healthy adult cats with a mean (± SD)
body weight of 4.1 ± 0.44 kg.
Procedure—CBC determination and biochemical
analysis of blood samples were performed for all cats.
Cats were anesthetized by use of isoflurane, and
catheters were placed IV in a central vein. The next
day, blood samples were obtained from the catheters
before and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after
applying a 4% liposome-encapsulated lidocaine
cream (15 mg/kg) to a clipped area over the cephalic
vein. Plasma concentrations of lidocaine were analyzed
with a high-performance liquid chromatography
Results—Two cats had minimal transdermal absorption
of lidocaine, with lidocaine concentrations below
the sensitivity of the assay at all but 1 or 2 time
points. In the other 4 cats, the median maximum plasma
concentration was 149.5 ng/ml, the median time
to maximum plasma concentration was 2 hours, and
the median area under the concentration versus time
curve from zero to infinity was 1014.5 ng·h/ml.
Conclusions and Clinical Relevance—Maximum
plasma concentrations of lidocaine remained substantially
below toxic plasma concentrations for cats.
On the basis of these data, topical administration of a
liposome-encapsulated lidocaine formulation at a
dose of 15 mg/kg appears to be safe for use in healthy
adult cats. (Am J Vet Res 2002;63:1309–1312)
Objective—To determine the pharmacokinetics and clinical effects of a subanesthetic, continuous rate infusion of ketamine administered to healthy awake horses.
Animals—8 adult horses.
Procedures—Ketamine hydrochloride was administered to 2 horses, in a pilot study, at rates ranging from 0.4 to 1.6 mg/kg/h for 6 hours to determine an appropriate dose that did not cause adverse effects. Ketamine was then administered to 6 horses for a total of 12 hours (3 horses at 0.4 mg/kg/h for 6 hours followed by 0.8 mg/kg/h for 6 hours and 3 horses at 0.8 mg/kg/h for 6 hours followed by 0.4 mg/kg/h for 6 hours). Concentration of ketamine in plasma, heart rate, respiratory rate, blood pressure, physical activity, and analgesia were measured prior to, during, and following infusion. Analgesic testing was performed with a modified hoof tester applied at a measured force to the withers and radius.
Results—No signs of excitement and no significant changes in the measured physiologic variables during infusion rates of 0.4 and 0.8 mg of ketamine/kg/h were found. At 6 hours following infusions, heart rate and mean arterial pressure were decreased, compared with preinfusion measurements. An analgesic effect could not be demonstrated during or after infusion. Pharmacokinetic variables for 0.4 and 0.8 mg/kg/h infusions were not significantly different.
Conclusions and Clinical Relevance—Ketamine can be administered to awake horses at 0.4 or 0.8 mg/kg/h without adverse behavioral effects. The observed pharmacokinetic values are different than those reported for single-dose IV bolus administration of this drug.