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Kauffman CA . Changing epidemiology of rare mould infections: implications for therapy . Drugs 2007 ; 67 : 1803 – 1812 . 10.2165/00003495-200767130-00001 2. Shao PL Huang LM Hsueh PR . Recent advances and challenges in the treatment of

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in American Journal of Veterinary Research

Abstract

Objective

To compare serum and skin concentrations of enrofloxacin in dogs with pyoderma with those of clinically normal dogs and to evaluate concentrations in dogs with superficial versus deep pyoderma.

Animals

16 clinically normal dogs and 16 dogs with pyoderma.

Procedure

Enrofloxacin (approx 5 mg/kg of body weight, PO) was administered daily to all dogs. Serum samples and skin biopsy specimens were obtained on day 1 at 3 hours after drug administration and on day 3 immediately before and 3 hours after drug administration. Samples and specimens were assayed by high-performance liquid chromatography. Morphometric analysis was performed on skin biopsy specimens to determine correlation between inflammatory cells and peak tissue enrofloxacin concentration on day 1.

Results

Morphometric analysis revealed high correlation between dermal inflammatory cell count and drug concentration in dogs with pyoderma.

Conclusions

At mean dosage of 5 mg/kg once daily, enrofloxacin tissue concentrations were significantly greater in dogs with pyoderma at 3 hours after pill administration. Enrofloxacin tissue concentration on day 3 at 3 hours after pill administration was 12.4 times the 90% minimum inhibitory concentration of enrofloxacin for Staphylococcus intermedius.

Clinical Relevance

In dogs with pyoderma, therapeutic tissue concentrations of enrofloxacin are reached as early as 3 hours after drug administration. (Am J Vet Res 1998;59:1599-1604)

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in American Journal of Veterinary Research

SUMMARY

The isoflurane-sparing effect of the α2-adrenergic agonist medetomidine (30 μg/kg of body weight, IV) was tested in 7 dogs, using a blinded, randomized-block study design. The baseline minimal alveolar concentration (mac) of isoflurane was 1.18 vol% (95% confidence interval [097,1.39])- Medetomidine significantly (P < 0.003) reduced isoflurane mac by 47.2%. Atipamezolc (0.3 mg/kg, iv), an α2-adrenergic antagonist, completely reversed the effect of mcdetomidine on isoflurane mac. Atipamezole alone did not significantly alter isoflurane mac.

After medetomidine administration, marked bradycardia developed in all dogs and persisted for more than 2 hours Mean arterial blood pressure increased acutely, but later decreased, and hypotension persisted for more than 2 hours. Atipamezole reversed the bradycardic and hypotensive effects of medetomidine.

Results of this study indicate that medetomidine mav be useful in clinical cases in which isoflurane mac-reduction is desirable and that atipamezole might be used to reverse desirable and undesirable effects of medetomidine during isoflurane anesthesia.

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in American Journal of Veterinary Research

Abstract

OBJECTIVE

To evaluate the pharmacokinetics of hydromorphone hydrochloride after IM and IV administration to orange-winged Amazon parrots (Amazona amazonica).

ANIMALS

8 orange-winged Amazon parrots (4 males and 4 females).

PROCEDURES

Hydromorphone (1 mg/kg) was administered once IM. Blood samples were collected 5 minutes and 0.5, 1.5, 2, 3, 6, and 9 hours after drug administration. Plasma hydromorphone concentrations were determined with liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated with a compartmental model. The experiment was repeated 1 month later with the same dose of hydromorphone administered IV.

RESULTS

Plasma hydromorphone concentrations were > 1 ng/mL for 6 hours in 8 of 8 and 6 of 7 parrots after IM and IV injection, respectively. After IM administration, mean bioavailability was 97.6%, and mean maximum plasma concentration was 179.1 ng/mL 17 minutes after injection. Mean volume of distribution and plasma drug clearance were 4.24 L/kg and 64.2 mL/min/kg, respectively, after IV administration. Mean elimination half-lives were 1.74 and 1.45 hours after IM and IV administration, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE

Hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with rapid plasma clearance and a large volume of distribution after IV administration in orange-winged Amazon parrots. Drug elimination half-lives were short. Further pharmacokinetic studies of hydromorphone and its metabolites, including investigation of multiple doses, different routes of administration, and sustained-release formulations, are recommended.

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in American Journal of Veterinary Research

Abstract

OBJECTIVE

To identify an oral dose of grapiprant for red-tailed hawks (RTHAs; Buteo jamaicensis) that would achieve a plasma concentration > 164 ng/mL, which is considered therapeutic for dogs with osteoarthritis.

ANIMALS

6 healthy adult RTHAs.

PROCEDURES

A preliminary study, in which grapiprant (4 mg/kg [n = 2], 11 mg/kg [2], or 45 mg/kg [2]) was delivered into the crop of RTHAs from which food had been withheld for 24 hours, was performed to obtained pharmacokinetic data for use with modeling software to simulate results for grapiprant doses of 20, 25, 30, 35, and 40 mg/kg. Simulation results directed our selection of the grapiprant dose administered to the RTHAs in a single-dose study. Plasma grapiprant concentration, body weight, and gastrointestinal signs of RTHAs were monitored.

RESULTS

On the basis of results from the preliminary study and simulations, a grapiprant dose of 30 mg/kg was used in the single-dose study. The geometric mean maximum observed plasma concentration of grapiprant was 3,184 ng/mL, time to maximum plasma grapiprant concentration was 2.0 hours, and the harmonic mean terminal half-life was 17.1 hours. No substantial adverse effects were observed.

CONCLUSIONS AND CLINICAL RELEVANCE

Although the single dose of grapiprant (30 mg/kg) delivered into the crop achieved plasma concentrations > 164 ng/mL in the RTHAs, it was unknown whether this concentration would be therapeutic for birds. Further research that incorporates multidose assessments, safety monitoring, and pharmacodynamic data collection is warranted on the use of grapiprant in RTHAs from which food was withheld versus not withheld.

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in American Journal of Veterinary Research

Abstract

OBJECTIVE

To characterize the pharmacokinetics of mycophenolate mofetil (MMF) following single-dose IV or PO administration, characterize the pharmacokinetics of MMF following long-term PO administration, and describe the clinicopathologic effects of long-term MMF administration in horses.

ANIMALS

12 healthy adult horses.

PROCEDURES

In phase 1, 6 horses received a single IV (2.5 mg/kg) or PO (5 mg/kg) dose of MMF in a randomized balanced crossover assessment (≥ 2-week interval between administrations). In phase 2, 6 other horses received MMF for 60 days (5 mg/kg, PO, q 24 h for 30 days and then 5 mg/kg, PO, q 48 h for an additional 30 days).

RESULTS

Following IV (single-dose) or PO (single- or multiple-dose) administration, MMF was rapidly converted to mycophenolic acid. For single-dose PO administration, mean ± SD maximum plasma mycophenolic acid concentration was 1,778.3 ± 441.5 ng/mL at 0.71 ± 0.29 hours. For single-dose IV administration, mean systemic clearance and volume of distribution at steady state were 0.689 ± 0.194 L/h/kg and 1.57 ± 0.626 L/kg, respectively. Following single doses, mean terminal half-life was 3.99 ± 0.865 hours for IV administration and 4.02 ± 1.01 hours for PO administration. The accumulation index following long-term PO administration was 1.0 ± 0.002, and the terminal half-life was 4.59 ± 1.25 hours following the final dose on day 60. None of the horses developed abnormal clinical signs or had any consistently abnormal clinicopathologic findings.

CONCLUSIONS AND CLINICAL RELEVANCE

Further investigation of the clinical efficacy of long-term MMF treatment of horses with autoimmune diseases is warranted.

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in American Journal of Veterinary Research

Abstract

Objective

To determine whether oral administration of erythromycin alters the inflammatory response to bronchoalveolar lavage (BAL) in young horses.

Animals

12 healthy, unweaned, mixed-breed foals of either sex, between 2 and 4 months old.

Procedure

BAL was performed; 250 ml of phosphate-buffered saline solution (300 mOsm, pH 7.4) was administered in 50-ml aliquots. Foals were carefully monitored for 4 days, then erythromycin base (25 mg/kg of body weight, PO, q 12 h) was given to foals of the treated group. After 4 days, foals were re-anesthetized, and the same lung was relavaged. Cytologic examination was performed on BAL fluid (BALF) samples from both groups of foals. At 12 hours after administration of the final dose, erythromycin A and anhydroerythromycin A concentrations were determined in plasma of treated foals.

Results

In the second BALF sample from the same lung of control foals, percentage of neutrophils was significantly increased (3 ± 38.0%), compared with that from erythromycin-treated foals (4.88 ± 3.66%, P < 0.05), and was associated with apparent decrease in the ability of BALF cells from erythromycin-treated foals to migrate toward a chemoattractant source. Significantly fewer BALF cells adhered to a cell culture substratum after erythromycin treatment of foals. Erythromycin A was not detected in plasma of any treated foal at the time of the second BAL; anhydroerythromycin A, a degradation product of erythromycin, was detected in plasma of 5 of 6 foals (mean concentration, 0.2 ± 0.06 µg/ml).

Conclusion and Clinical Relevance

BAL induces neutrophilic inflammation, which persists for at least 4 days in the lungs of young horses. Erythromycni (25 mg/kg, PO, q 12 h) diminishes this inflammatory response through a mechanism that may involve alteration of BALF cell function. Degradation of erythromycin to biologically active products or presence of parent drug in pulmonary secretions may be responsible for alterations in pulmonary lavage cell Chemotaxis and adherence. Erythromycin administered orally to foals at clinically relevant doses appears to have nonantimicrobial effects that may interfere with host cell metabolism and decrease inflammatory reponses in airways. (Am J Vet Res 1997;58:56–61)

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in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine the pharmacokinetics and adverse effects at the injection site of ceftiofur crystalline-free acid (CCFA) following IM administration of 1 dose to red-tailed hawks (Buteo jamaicensis).

ANIMALS 7 adult nonreleasable healthy red-tailed hawks.

PROCEDURES In a randomized crossover study, CCFA (10 or 20 mg/kg) was administered IM to each hawk and blood samples were obtained. After a 2-month washout period, administration was repeated with the opposite dose. Muscle biopsy specimens were collected from the injection site 10 days after each sample collection period. Pharmacokinetic data were calculated. Minimum inhibitory concentrations of ceftiofur for various bacterial isolates were assessed.

RESULTS Mean peak plasma concentrations of ceftiofur-free acid equivalent were 6.8 and 15.1 μg/mL for the 10 and 20 mg/kg doses, respectively. Mean times to maximum plasma concentration were 6.4 and 6.7 hours, and mean terminal half-lives were 29 and 50 hours, respectively. Little to no muscle inflammation was identified. On the basis of a target MIC of 1 μg/mL and target plasma ceftiofur concentration of 4 μg/mL, dose administration frequencies for infections with gram-negative and gram-positive organisms were estimated as every 36 and 45 hours for the 10 mg/kg dose and every 96 and 120 hours for the 20 mg/kg dose, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE Study results suggested that CCFA could be administered IM to red-tailed hawks at 10 or 20 mg/kg to treat infections with ceftiofur-susceptible bacteria. Administration resulted in little to no inflammation at the injection site. Additional studies are needed to evaluate effects of repeated CCFA administration.

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in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics of ceftiofur crystalline-free acid (CCFA) following SC administration of a single dose to sheep.

Animals—9 healthy adult female Suffolk-crossbred sheep.

Procedures—Each sheep was administered 6.6 mg of CCFA/kg, SC, in the cervical region once. Serial blood samples were collected at predetermined intervals for 14 days. Serum concentration of ceftiofur free-acid equivalents (CFAE) was determined by high-performance liquid chromatography. Pharmacokinetic parameters were determined by compartmental and noncompartmental methods.

Results—Pharmacokinetics for CCFA following SC administration in sheep was best described with a 1-compartment model. Mean ± SD area under the concentration-time curve from time 0 to infinity, peak serum concentration, and time to peak serum concentration were 206.6 ± 24.8 μ•h/mL, 2.4 ± 0.5 μg/mL, and 23.1 ± 10.1 h, respectively. Serum CFAE concentrations ≥ 1 μg/mL (the target serum CFAE concentration for treatment of disease caused by Mannheimia haemolytica and Pasteurella multocida) were maintained for 2.6 to 4.9 days. No significant adverse reactions to CCFA administration were observed.

Conclusions and Clinical Relevance—Results indicated that adequate therapeutic serum concentrations of CFAE for treatment of disease caused by M haemolytica and P multocida were achieved in sheep following SC administration of a single dose (6.6 mg/kg) of CCFA. Thus, CCFA might be useful for the treatment of common respiratory tract pathogens in sheep.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To compare the pharmacokinetics of 2 commercial florfenicol formulations following IM and SC administration to sheep.

ANIMALS 16 healthy adult mixed-breed sheep.

PROCEDURES In a crossover study, sheep were randomly assigned to receive florfenicol formulation A or B at a single dose of 20 mg/kg, IM, or 40 mg/kg, SC. After a 2-week washout period, each sheep was administered the opposite formulation at the same dose and administration route as the initial formulation. Blood samples were collected immediately before and at predetermined times for 24 hours after each florfenicol administration. Plasma florfenicol concentrations were determined by high-performance liquid chromatography. Pharmacokinetic parameters were estimated by noncompartmental methods and compared between the 2 formulations at each dose and route of administration.

RESULTS Median maximum plasma concentration, elimination half-life, and area under the concentration-time curve from time 0 to the last quantifiable measurement for florfenicol were 3.76 μg/mL, 13.44 hours, and 24.88 μg•h/mL, respectively, for formulation A and 7.72 μg/mL, 5.98 hours, and 41.53 μg•h/mL, respectively, for formulation B following administration of 20 mg of florfenicol/kg, IM, and 2.63 μg/mL, 12.48 hours, and 31.63 μg•h/mL, respectively, for formulation A and 4.70 μg/mL, 16.60 hours, and 48.32 μg•h/mL, respectively, for formulation B following administration of 40 mg of florfenicol/kg, SC.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that both formulations achieved plasma florfenicol concentrations expected to be therapeutic for respiratory tract disease caused by Mannheimia haemolytica or Pasteurella spp at both doses and administration routes evaluated.

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in American Journal of Veterinary Research