Objective—To determine concentrations of marbofloxacin
in alveolar macrophages (AMs) and epithelial
lining fluid (ELF) and compare those concentrations
with plasma concentrations in healthy dogs.
Animals—12 adult mixed-breed and purebred
Procedure—10 dogs received orally administered marbofloxacin
at a dosage of 2.75 mg/kg every 24 hours for
5 days. Two dogs served as nontreated controls.
Fiberoptic bronchoscopy and bronchoalveolar lavage
procedures were performed while dogs were anesthetized
with propofol, approximately 6 hours after the
fifth dose. The concentrations of marbofloxacin in plasma
and bronchoalveolar fluid (cell and supernatant fractions)
were determined by use of high-performance liquid
chromatography with detection of fluorescence.
Results—Mean ± SD plasma marbofloxacin concentrations
2 and 6 hours after the fifth dose were 2.36 ±
0.52 µg/mL and 1.81 ± 0.21 µg/mL, respectively.
Mean ± SD marbofloxacin concentration 6 hours after
the fifth dose in AMs (37.43 ± 24.61 µg/mL) was significantly
greater than that in plasma (1.81 ± 0.21
µg/mL) and ELF (0.82 ± 0.34 µg/mL), resulting in a
mean AM concentration-to-plasma concentration
ratio of 20.4, a mean AM:ELF ratio of 60.8, and a
mean ELF-to-plasma ratio of 0.46. Marbofloxacin was
not detected in any samples from control dogs.
Conclusions and Clinical Relevance—Marbofloxacin
concentrations in AMs were greater than the mean
inhibitory concentrations of major bacterial pathogens
in dogs. Results indicated that marbofloxacin accumulates
in AMs at concentrations exceeding those
reached in plasma and ELF. The accumulation of marbofloxacin
in AMs may facilitate treatment for susceptible
intracellular pathogens or infections associated
with pulmonary macrophage infiltration. (Am J Vet Res
Objective—To evaluate efficacy and safety of using
transdermal fentanyl patches (TFP) for analgesia in
cats undergoing onychectomy.
Design—Randomized controlled clinical trial.
Animals—45 client-owned cats weighing ≥ 2.7 kg
(5.9 lb) undergoing onychectomy, onychectomy and
ovariohysterectomy, or onychectomy and castration.
Procedure—Cats were randomly assigned to be
treated with a TFP (25 µg/h) or butorphanol; TFP were
applied a minimum of 4 hours before surgery (approx
8 hours prior to extubation). Rectal temperature, heart
rate, respiratory rate, force applied by the forelimbs,
and serum fentanyl concentration were measured,
and temperament, recovery, degree of sedation,
severity of pain, severity of lameness, and appetite
were scored before and periodically for up to 40 hours
Results—Cats treated with a TFP had better recovery
scores at 2 of 4 evaluation times, lower sedation
scores at 2 of 8 evaluation times, and lower pain
scores at 6 of 8 evaluation times, compared with cats
treated with butorphanol. Use of a pressure-sensitive
mat to evaluate force applied by the forelimbs did not
reveal any differences between groups but did reveal
a significant difference between preoperative and
postoperative values. Mean ± SD serum fentanyl concentrations
were 1.56 ± 1.08, 4.85 ± 2.38, 4.87 ± 1.56,
and 4.35 ± 2.97 ng/ml approximately 8, 24, 32, and 48
hours, respectively, after TFP placement.
Conclusion and Clinical Relevance—Results suggest
that use of a TFP (25 µg/h) for postoperative analgesia
in cats undergoing onychectomy with or without
surgical sterilization is safe and effective. (J Am
Vet Med Assoc 2000;217:1013–1020)
Objective—To evaluate differences in bacterial numbers,
identity, and susceptibility in samples obtained
from the tympanic cavity on entry (preflush) and after
evacuation and lavage (postflush) and assess perioperative
and empiric antimicrobial selection in dogs
that underwent total ear canal ablation (TECA) with
lateral bulla osteotomy (LBO) or reoperation LBO.
Design—Prospective clinical study.
Procedure—TECA with LBO or reoperation LBO was
performed on 47 ears. Pre- and postflush aerobic and
anaerobic samples were obtained from the tympanic
cavity. Isolates and antimicrobial susceptibility patterns
Results—Different isolates (31/44 [70%] ears) and susceptibility
patterns of isolate pairs (6/44 [14%] ears)
were detected in pre- and postflush samples from
84% of ears. Evacuation and lavage of the tympanic
cavity decreased the number of bacterial isolates by
33%. In 26% of ears, bacteria were isolated from postflush
samples but not preflush samples. Only 26% of
isolates tested were susceptible to cefazolin. At least 1
isolate from 53% of dogs that received empirically chosen
antimicrobials postoperatively was resistant to the
selected drugs. Anaerobic bacteria were recovered
from 6 ears.
Conclusions and Clinical Relevance—Accurate
microbiologic assessment of the tympanic cavity
should be the basis for selection of antimicrobials in
dogs undergoing TECA with LBO. Bacteria remain in
the tympanic cavity after evacuation and lavage.
Cefazolin was a poor choice for dogs that underwent
TECA with LBO, as judged on the basis of culture and
susceptibility testing results. (J Am Vet Med Assoc 2005;227:748–755)
Objective—To describe the disposition of and pharmacodynamic response to atenolol when administered as a novel transdermal gel formulation to healthy cats.
Animals—7 healthy neutered male client-owned cats.
Procedures—Atenolol was administered either orally as a quarter of a 25-mg tablet or as an equal dose by transdermal gel. Following 1 week of treatment, an ECG and blood pressure measurements were performed and blood samples were collected for determination of plasma atenolol concentration at 2 and 12 hours after administration.
Results—2 hours after oral administration, 6 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 579 ± 212 ng/mL. Two hours following transdermal administration, only 2 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 177 ± 123 ng/mL. The difference in concentration between treatments was significant. Trough plasma atenolol concentrations of 258 ± 142 ng/mL and 62.4 ± 17 ng/mL were achieved 12 hours after oral and transdermal administration, respectively. A negative correlation was found between heart rate and plasma atenolol concentration.
Conclusions and Clinical Relevance—Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.
Objective—To determine whether trilostane or ketotrilostane is more potent in dogs and determine the trilostane and ketotrilostane concentrations that inhibit adrenal gland cortisol, corticosterone, and aldosterone secretion by 50%.
Sample—24 adrenal glands from 18 mixed-breed dogs.
Procedures—Adrenal gland tissues were sliced, placed in tissue culture, and stimulated with 100 pg of ACTH/mL alone or with 5 concentrations of trilostane or ketotrilostane. Trials were performed independently 4 times. In each trial, 6 samples (1 for each time point) were collected for each of the 5 concentrations of trilostane and ketotrilostane tested as well as a single negative control samples. At the end of 0, 1, 2, 3, 5, and 7 hours, tubes were harvested and media and tissue slices were assayed for cortisol, corticosterone, aldosterone, and potassium concentrations. Data were analyzed via pharmacodynamic modeling. One adrenal slice exposed to each concentration of trilostane or ketotrilostane was submitted for histologic examination to assess tissue viability.
Results—Ketotrilostane was 4.9 and 2.4 times as potent in inhibiting cortisol and corticosterone secretion, respectively, as its parent compound trilostane. For trilostane and ketotrilostane, the concentrations that inhibited secretion of cortisol or corticosterone secretion by 50% were 480 and 98.4 ng/mL, respectively, and 95.0 and 39.6 ng/mL, respectively.
Conclusions and Clinical Relevance—Ketotrilostane was more potent than trilostane with respect to inhibition of cortisol and corticosterone secretion. The data should be useful in developing future studies to evaluate in vivo serum concentrations of trilostane and ketotrilostane for efficacy in the treatment of hyperadrenocorticism.
Objective—To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose of amikacin administered via regional IV limb perfusion (RILP) in standing horses.
Animals—14 adult horses.
Procedures—Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb. Samples of interstitial fluid (collected via implanted capillary ultrafiltration devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joint were collected prior to (time 0) and at intervals after tourniquet release for determination of drug concentrations. For pharmacokinetic-pharmacodynamic analyses, minimum inhibitory concentrations (MICs) of 16 μg/mL (amikacin) and 0.5 μg/mL (enrofloxacin) were applied.
Results—After RILP with enrofloxacin, 3 horses developed vasculitis. The highest synovial fluid concentrations of enrofloxacin and amikacin were detected at time 0; median values (range) were 13.22 μg/mL (0.254 to 167.9 μg/mL) and 26.2 μg/mL (5.78 to 50.0 μg/mL), respectively. Enrofloxacin concentrations exceeded MIC for approximately 24 hours in STIF and synovial fluid and for 36 hours in BMIF. After perfusion of amikacin, concentrations greater than the MIC were not detected in any samples. Effective therapeutic concentrations of enrofloxacin were attained in all samples.
Conclusions and Clinical Relevance—In horses with orthopedic infections, RILP of enrofloxacin (1.5 mg/kg) should be considered as a treatment option. However, care must be taken during administration. A dose of amikacin > 250 mg is recommended to attain effective tissue concentrations via RILP in standing horses.
OBJECTIVE To evaluate pharmaceutical characteristics (strength or concentration, accuracy, and precision), physical properties, and bacterial contamination of fluconazole compounded products.
SAMPLE Fluconazole compounded products (30- and 240-mg capsules; 30- and 100-mg/mL oral suspensions) from 4 US veterinary compounding pharmacies.
PROCEDURES Fluconazole compounded products were ordered 3 times from each of 4 pharmacies at 7- or 10-day intervals. Generic fluconazole products (50- and 200-mg tablets; 10- and 40-mg/mL oral suspensions) served as references. Compounded products were evaluated at the time of receipt; suspensions also were evaluated 3 months later and at beyond-use dates. Evaluations included assessments of strength (concentration), accuracy, precision, physical properties, and bacterial contamination. Acceptable accuracy was defined as within ± 10% of the labeled strength (concentration) and acceptable precision as within ± 10%. Fluconazole was quantified by use of high-performance liquid chromatography.
RESULTS Physical characteristics of compounded products differed among pharmacies. Aerobic bacterial cultures yielded negative results. Capsules (30 and 240 mg) had acceptable accuracy (median, 96.3%; range, 87.3% to 135.2%) and precision (mean ± SD, 7.4 ± 6.0%). Suspensions (30 and 100 mg/mL) had poor accuracy (median, 73.8%; range, 53.9% to 95.2%) and precision (mean ± SD, 15.0 ± 6.9%). Accuracy and precision were significantly better for capsules than for suspensions.
CONCLUSIONS AND CLINICAL RELEVANCE Fluconazole compounded products, particularly suspensions, differed in pharmaceutical and physical qualities. Studies to evaluate the impact of inconsistent quality on bioavailability or clinical efficacy of compounded fluconazole products are indicated, and each study should include data on the quality of the compounded product evaluated.
Objective—To investigate the contribution of gyrA mutation and efflux pumps to fluoroquinolone resistance and multidrug resistance among Escherichia coli isolates from dogs and cats.
Sample Population—536 clinical isolates of E coli.
Procedures—Minimum inhibitory concentrations (MICs) were determined for enrofloxacin and 6 other drug classes by use of broth microdilution techniques. Real-time PCR assay was used to determine the mutation in gyrA; Phe-Arg-β-naphthylamide, an efflux pump inhibitor, was used to examine the contribution of efflux pump overexpression.
Results—The MIC for fluoroquinolones increased in a stepwise fashion and was lowest in the absence of mutations, higher with a single point mutation, and highest with 2 point mutations. Level of resistance in the latter category was high (8 times the breakpoint), but this was associated with expression of the AcrAB efflux pump. Inhibition of the efflux pump resulted in a reduction in the MIC to less than the susceptible breakpoint for isolates with an MIC ≤ 4 mg/L, regardless of the presence of a mutation. The greatest magnitude in MIC decrease (MIC was decreased by a factor of > 67 fold) was for isolates with a single mutation but the greatest absolute decrease in MIC (124 mg/L) was for isolates with 2 mutations. Inhibition of the AcrAB efflux pump in isolates characterized by multidrug resistance decreased the MIC of drugs structurally unrelated to fluoroquinolone.
Conclusions and Clinical Relevance—Fluoroquinolone resistance in E coli appeared to be a stepwise phenomenon, with MIC increasing as the number of point mutations in gyrA increased, but high-level resistance and multidrug resistance associated with fluoroquinolone resistance reflected overexpression of the AcrAB efflux pump.
Objective—To evaluate disposition of butorphanol
after IV and IM administration, effects on physiologic
variables, and analgesic efficacy after IM administration
Design—Nonrandomized crossover study.
Animals—6 healthy adult male llamas.
Procedure—Butorphanol (0.1 mg/kg [0.045 mg/lb] of
body weight) was administered IM first and IV 1
month later. Blood samples were collected intermittently
for 24 hours after administration. Plasma butorphanol
versus time curves were subjected to pharmacokinetic
analysis. Two months later, butorphanol
(0.1 mg/kg) was administered IM, and physiologic
variables and analgesia were assessed.
Results—Extrapolated peak plasma concentrations
after IV and IM administration were 94.8 ± 53.1 and
34.3 ± 11.6 ng/ml, respectively. Volume of distribution
at steady state after IV administration was 0.822 ±
0.329 L/kg per minute and systemic clearance was
0.050 ± 0.014 L/kg per minute. Slope of the elimination
phase was significantly different, and elimination
half-life was significantly shorter after IV (15.9 ± 9.1
minutes) versus IM (66.8 ± 13.5 minutes) administration.
Bioavailability was 110 ± 49% after IM administration.
Heart rate decreased and rectal temperature
increased. Somatic analgesia was increased for various
periods. Two llamas became transiently sedated,
and 2 became transiently excited after butorphanol
Conclusions and Clinical Relevance—Although IV
administration of butorphanol results in a short halflife
that may limit its analgesic usefulness, the elimination
half-life of butorphanol administered IM is likely
to be clinically useful. The relationship among plasma
butorphanol concentration, time, and analgesia
differed with the somatic analgesia model; clinically
useful analgesia may occur at lower plasma concentrations
than those reported here. (J Am Vet Med
Objective—To evaluate the correlation between the
half-time of liquid-phase gastric emptying (T50) determined
by use of nuclear scintigraphy, using technetium
Tc 99m pentetate, and absorption variables of
orally administered acetaminophen in horses with
experimentally delayed gastric emptying.
Animals—6 mature horses.
Procedure—Delayed gastric emptying was induced
by IV injection of atropine sulfate. Twenty minutes
later, acetaminophen and technetium Tc 99m pentetate
were administered simultaneously via nasogastric
tube. Serial lateral images of the stomach region
were obtained, using a gamma camera. Power exponential
curves were used for estimation of T50 and
modified R2 values for estimation of goodness-of-fit of
the data. Serial serum samples were obtained, and
acetaminophen concentration was determined, using
fluorescence polarization immunoassay. Maximum
serum concentration (Cmax), time to reach maximum
serum concentration (Tmax), area under the curve for
480 minutes, and the appearance rate constant were
determined, using a parameter estimation program.
Correlations were calculated, using a Spearman rank
Results—A significant correlation was detected
between T50 determined by use of scintigraphy and
Tmax determined by use of acetaminophen absorption.
Correlation between T50 and other absorption
variables of acetaminophen was not significant.
Conclusions and Clinical Relevance—The acetaminophen
absorption method was a valid technique in
this model of delayed gastric emptying in horses. The
method may be a valuable tool for use in research as
well as in clinical evaluation of gastric emptying in
horses. (Am J Vet Res 2002;63:170–174)