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Abstract

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.

Animals—34 dogs.

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 were compared.

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)

Full access
in Journal of the American Veterinary Medical Association

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

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.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate disposition of butorphanol after IV and IM administration, effects on physiologic variables, and analgesic efficacy after IM administration in llamas.

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 administration.

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 Assoc 2001;219:1263–1267)

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective

To evaluate disposition of fentanyl in goats after IV and transdermal administration.

Animals

8 healthy 2-year-old goats weighing 31.8 to 53.6 kg (mean ± SD, 40.4 ± 7.5 kg).

Procedure

Each goat was given 2 treatments consisting of fentanyl administered IV (2.5 μg/kg of body weight) and via a transdermal patch (50 μg/h). There was a 2-month interval between treatments. Blood samples were collected at specified times and analyzed in duplicate to determine plasma fentanyl concentrations. Pharmacokinetic values were calculated, using a computerized modeling program.

Results

Administration of fentanyl was tolerated by all goats. Intravenous administration of fentanyl resulted in a transitory increase in rectal temperature that was not clinically important. Terminal elimination half-life after IV administration was 1.20 ± 0.78 h, volume of distribution at steady state was 1.51 ± 0.39 L/kg, and systemic clearance was 2.09 ± 0.62 L/kg/h. Transdermal administration of fentanyl resulted in variable plasma concentrations, with peak plasma concentrations ranging from 1.12 to 16.69 ng/ml (mean ± SD, 6.99 ± 6.03 ng/ml) and time to peak concentration ranging from 8 to 18 hours (mean ± SD, 13 ± 4.5 hours). After removal of the transdermal patch, mean ± SD terminal elimination half-life was 5.34 ± 5.34 hours.

Conclusions and Clinical Relevance

Intravenous administration of fentanyl (2.5 μg/kg) in goats results in a relatively short half-life that will limit its use for management of pain. Transdermal administration of fentanyl (50 μg/h) in goats results in variable plasma concentrations that may exceed those anticipated on the basis of a theoretical delivery rate, but stable plasma concentrations of fentanyl may not be achieved. (Am J Vet Res 1999;60:986–991)

Free access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To compare pharmacokinetics of levetiracetam in serum and CSF of cats after oral administration of extended-release (ER) levetiracetam.

ANIMALS

9 healthy cats.

PROCEDURES

Cats received 1 dose of a commercially available ER levetiracetam product (500 mg, PO). Thirteen blood and 10 CSF samples were collected over a 24-hour period for pharmacokinetic analysis. After 1 week, cats received 1 dose of a compounded ER levetiracetam formulation (500 mg, PO), and samples were obtained at the same times for analysis.

RESULTS

CSF concentrations of levetiracetam closely paralleled serum concentrations. There were significant differences between the commercially available product and the compounded formulation for mean ± SD serum maximum concentration (Cmax; 126 ± 33 μg/mL and 169 ± 51 μg/mL, respectively), Cmax corrected for dose (0.83 ± 0.10 μg/mL/mg and 1.10 ± 0.28 μg/mL/mg, respectively), and time to Cmax (5.1 ± 1.6 hours and 3.1 ± 1.5 hours, respectively). Half-life for the commercially available product and compounded formulation of ER levetiracetam was 4.3 ± 2.0 hours and 5.0 ± 1.6 hours, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE

The commercially available product and compounded formulation of ER levetiracetam both maintained concentrations in healthy cats 12 hours after oral administration that have been found to be therapeutic in humans (ie, 5 μg/mL). Results of this study supported dosing intervals of 12 hours, and potentially 24 hours, for oral administration of ER levetiracetam to cats. Monitoring of serum concentrations of levetiracetam can be used as an accurate representation of levetiracetam concentrations in CSF of cats.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To characterize the pharmacokinetics of a clinically relevant dose of misoprostol administered PO or per rectum (PR) to horses.

ANIMALS

8 healthy adult horses.

PROCEDURES

In a randomized 3-way crossover design, horses received a single dose of misoprostol (5 μg/kg) administered PO (with horses fed and unfed) and PR, with a minimum 3-week washout period separating the experimental conditions. Blood samples were obtained before and at various points after drug administration (total, 24 hours), and plasma concentrations of misoprostol free acid were measured.

RESULTS

Mean maximum plasma concentration of misoprostol was significantly higher in the PR condition (mean ± SD, 967 ± 492 pg/mL) and unfed PO condition (655 ± 259 pg/mL) than in the fed PO condition (352 ± 109 pg/mL). Mean area under the concentration-versus-time curve was significantly lower in the PR condition (219 ± 131 pg•h/mL) than in the unfed (1,072 ± 360 pg•h/mL) and fed (518 ± 301 pg•h/mL) PO conditions. Mean time to maximum concentration was ≤ 30 minutes for all conditions. Mean disappearance half-life was shortest in the PR condition (21 ± 29 minutes), compared with values for the unfed (170 ± 129 minutes) and fed (119 ± 51 minutes) PO conditions. No adverse effects were noted.

CONCLUSIONS AND CLINICAL RELEVANCE

Misoprostol was rapidly absorbed and eliminated regardless of whether administered PO or PR to horses. Rectal administration may be a viable alternative for horses that cannot receive misoprostol PO, but this route may require more frequent administration to maintain therapeutic drug concentrations.

Full access
in American Journal of Veterinary Research