Introduction: The purpose of this study was to investigate the therapeutic effect of hydrogen on the therapy of onion poisoned dogs. Material and Methods: A total of 16 adult beagle dogs were divided into two groups (control and hydrogen) and all were fed dehydrated onion powder at the dose of 10 g/kg for three days. The dogs of the experimental group were given subcutaneous injection of 0.2 mL/kg of hydrogen for 12 days after making the poisoned model successful. Blood samples were collected before feeding onions, one day before injecting hydrogen, and 2 h after the injection of hydrogen on days 1, 3, 5, 7, 9, and 12. Control dogs were not treated with hydrogen. Results: The levels of leukocyte production, anaemia, red blood cell degeneration which was reflected by the values of Heinz body count, haemolytic ratio, and oxidative products in hydrogen treated group were lower than in control dogs on some days. The capacity of medullary haematopoiesis that was based on reticulocyte counts, and the antioxidation in hydrogen group were higher compared with control group. However, the differences in renal function were not obvious in both groups. Conclusion: Accordingly, it was concluded that subcutaneous injection of hydrogen could alleviate the symptoms in onion poisoned dogs.

OBJECTIVE To determine the pharmacokinetics of cefovecin sodium after SC administration of a single dose to African lions (Panthera leo). ANIMALS 3 adult (9 to 10 years old; 1 male and 2 females) and 3 juvenile (2 years old; 1 male and 2 females) African lions. PROCEDURES A crossover study was conducted. A single dose of cefovecin was administered SC at 4 mg/kg (half dose) and 8 mg/kg (full dose) to African lions. Blood samples were collected daily for 14 days after cefovecin injection. Plasma drug concentrations were determined by use of high-performance liquid chromatography with UV detection. RESULTS Cefovecin had first-order elimination kinetics for doses of 4 and 8 mg/kg. Mean ± SD maximum plasma concentration was 9.73 ± 1.01 μg/mL and 18.35 ± 0.94 μg/mL after doses of 4 and 8 mg/kg, respectively. Time to maximum plasma concentration was approximately 4 hours for both doses. Mean elimination half-life was approximately 111 and 115 hours after doses of 4 and 8 mg/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Cefovecin was detected in lion plasma for 336 hours after administration at both 4 and 8 mg/kg at concentrations greater than the reported minimum inhibitory concentration (0.06 μg/mL) for common bacterial organisms in domestic cats. These results indicated that cefovecin administered at 4 mg/kg SC reached therapeutic concentrations for an extended period in African lions.

OBJECTIVE To determine plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin following single-dose SC administration to black-tailed prairie dogs (Cynomys ludovicianus). ANIMALS 8 captive healthy 6-month-old sexually intact male black-tailed prairie dogs. PROCEDURES Enrofloxacin (20 mg/kg) was administered SC once to 6 prairie dogs and IV once to 2 prairie dogs. A blood sample was collected from each animal immediately before (0 hours) and 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration to evaluate the pharmacokinetics of enrofloxacin and ciprofloxacin. Plasma enrofloxacin and ciprofloxacin concentrations were quantified with ultraperformance liquid chromatography–mass spectrometry, and noncompartmental pharmacokinetic analysis was performed. RESULTS Enrofloxacin was biotransformed to ciprofloxacin in the prairie dogs used in the study. For total fluoroquinolones (enrofloxacin and ciprofloxacin), the mean (range) of peak plasma concentration, time to maximum plasma concentration, and terminal half-life after SC administration were 4.90 μg/mL (3.44 to 6.08 μg/mL), 1.59 hours (0.5 to 2.00 hours), and 4.63 hours (4.02 to 5.20 hours), respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that administration of enrofloxacin (20 mg/kg, SC, q 24 h) in black-tailed prairie dogs may be appropriate for treatment of infections with bacteria for which the minimum inhibitory concentration of enrofloxacin is ≤ 0.5 μg/mL. However, clinical studies are needed to determine efficacy of such enrofloxacin treatment.

OBJECTIVE To determine the concentration of tilmicosin in mammary gland secretions of dairy cows following administration of an experimental preparation once or twice during the dry period (45-day period immediately prior to calving during which cows are not milked) and to evaluate its efficacy for the treatment of cows with intramammary infections (IMIs) caused by Staphylococcus aureus at dry off (cessation of milking; first day of dry period), compared with that of an intramammary infusion of ceftiofur. ANIMALS 172 cows. PROCEDURES Milk samples were collected for microbiological culture 5 days before dry off and at calving and 15 and 30 days after calving. Cows with Staphylococcus IMIs were randomly assigned to receive an experimental preparation of tilmicosin (20 mg/kg, SC) once at dry off (n = 58) or at dry off and again 20 days later (56) or receive a long-acting intramammary preparation of ceftiofur (500 mg/mammary gland; 56) at dry off. Mammary gland secretions were collected from 5 cows in the tilmicosin-treated groups every 5 days after dry off until calving for determination of tilmicosin concentration. RESULTS Mean maximum concentration of tilmicosin in mammary gland secretions ranged from 14.4 to 20.9 μg/mL after the first dose and was 17.1 μg/mL after the second dose. The bacteriologic cure rate was 100% for all 3 treatments. Tilmicosin was detectable for 0 and 18 days after calving in the milk of cows treated with 1 and 2 doses of tilmicosin, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Administration of an experimental preparation of tilmicosin (20 mg/kg, SC) once to dairy cows at dry off might be useful for the treatment of S aureus IMIs.

Objective—To determine pharmacokinetics of marbofloxacin in water buffalo calves (Bubalus bubalis) after multiple SC administrations and to assess differences in regimen efficacy. Animals—18 healthy buffalo calves. Procedures—Calves (n = 6 calves/group) were assigned to receive marbofloxacin SC in the neck at 1 of 3 dosages (2 mg/kg, q 24 h for 6 days [regimen 1]; 4 mg/kg, q 48 h for 6 days [regimen 2]; and 4 mg/kg, q 24 h for 3 days [regimen 3]). Serum marbofloxacin concentrations were analyzed. Efficacy predictors were estimated on the basis of minimum inhibitory concentration and mutant prevention concentration reported for Pasteurella multocida and Mannheimia haemolytica. Results—Mean ± SD area under the concentration-time curve was 5.92 ± 0.40 μg•h/mL for regimen 1, which differed significantly from that for regimens 2 (14.26 ± 0.92 μg•h/mL) and 3 (14.17 ± 0.51 μg•h/mL). Mean residence time and mean elimination half-life for regimen 2 (9.93 ± 0.20 hours and 8.77 ± 0.71 hours) both differed significantly from those for regimens 1 (721 ± 0.11 hours and 5.71 ± 0.38 hours) and 3 (759 ± 0.13 hours and 737 ± 1.19 hours). Values obtained from indices for P multocida and M haemolytica had an excessively wide range because of the various degrees of antimicrobial susceptibility (low, medium, and high) of the strains. Conclusions and Clinical Relevance—Regimen 3 had the most favorable indices, and it would be conducive for owner compliance and require less handling of animals.

Objective: To measure florfenicol concentrations in ovine tear fluid after IM and SC administration and determine minimum inhibitory concentrations (MICs) of florfenicol against field isolates of Mycoplasma organisms potentially involved in infectious keratoconjunctivitis. Animals: 9 healthy adult Lacaune ewes. Procedures: Animals received an IM and SC administration of florfenicol (20 mg/kg) in a 2-way crossover design. Samples of blood and tear fluid were collected before and for 24 hours after administration. Concentrations of florfenicol in plasma and tear fluid were measured via high-performance liquid chromatography. The MIC of florfenicol for various Mycoplasma strains cultured from sheep and goats was determined via an agar dilution method. Results: Mean florfenicol concentration in tear fluid for the 24-hour period was significantly higher after IM administration (0.70 μg/mL) than after SC administration (0.22 μg/mL) and was maintained for a longer duration. The lacrimal fluid-to-plasma concentration ratio was not different between the 2 routes of administration, with mean values of 40.2% and 32.5% after IM and SC administration, respectively. The MIC for Mycoplasma agalactiae, Mycoplasma conjunctivae, and Mycoplasma mycoides isolates ranged from 0.5 to 8 μg of florfenicol/mL. Two strains of M agalactiae could be considered resistant to florfenicol. Conclusions and Clinical Relevance: Florfenicol readily penetrated the preocular tear fluid of sheep after IM and SC administration. For both routes of administration, doses > 20 mg/kg would be necessary to achieve tear fluid concentrations of florfenicol greater than the MICs for most strains of Mycoplasma organisms.

Objective—To compare the efficacy and adverse effects of sustained-release (SR) buprenorphine following SC administration and buprenorphine following oral transmucosal (OTM) administration in cats undergoing ovariohysterectomy. Animals—21 young healthy female cats. Procedures—As part of anesthetic premedication (0 hours), 10 cats received buprenorphine (0.02 mg/kg) via OTM administration with additional doses at 12, 24, 36, 48, and 60 hours and 11 cats received an equivalent total dose as a single SC injection of SR buprenorphine (0.12 mg/kg). The SR product contained buprenorphine hydrochloride in a proprietary SR matrix. All other anesthetic drugs and a single postoperative dose of meloxicam were administered similarly to all cats. Behavioral and physiologic variables were recorded, and signs of pain were assessed by use of 2 pain assessment scales and von anesthesia (RFA), and at 12, 24, 36, 48, 60, and 72 hours. Results—Heart rate increased and temperature (determined via microchip transponder thermometry) decreased from baseline values during RFA in both groups. Compared with baseline values, pain scores were increased during RFA and at the 12- and 24-hour time points in both groups; von Frey scores were higher during RFA. Behavioral and physiologic variables did not differ significantly between groups at any time point. Conclusions and Clinical Relevance—In cats undergoing ovariohysterectomy, SC administration of a preoperative dose of SR buprenorphine appeared to have comparable efficacy and adverse effect profile as that of twice-daily OTM administration of buprenorphine before and after surgery.

Objective-To estimate pharmacokinetic variables and measure tissue fluid concentrations of meropenem after IV and SC administration in dogs. Animals-6 healthy adult dogs. Procedure-Dogs were administered a single dose of meropenem (20 mg/kg) IV and SC in a crossover design. To characterize the distribution of meropenem in dogs and to evaluate a unique tissue fluid collection method, an in vivo ultrafiltration device was used to collect interstitial fluid. Plasma, tissue fluid, and urine samples were analyzed by use of high-performance liquid chromatography. Protein binding was determined by use of an ultrafiltration device. Results-Plasma data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean +/- SD values for half-life, volume of distribution, and clearance after IV administration for plasma samples were 0.67 +/- 0.07 hours, 0.372 +/- 0.053 L/kg, and 6.53 +/- 1.51 mL/min/kg, respectively, and half-life for tissue fluid samples was 1.15 +/- 0.57 hours. Half-life after SC administration was 0.98 +/- 0.21 and 1.31 +/- 0.54 hours for plasma and tissue fluid, respectively. Protein binding was 11.87%, and bioavailability after SC administration was 84%. Conclusions and Clinical Relevance-Analysis of our data revealed that tissue fluid and plasma (unbound fraction) concentrations were similar. Because of the kinetic similarity of meropenem in the extravascular and vascular spaces, tissue fluid concentrations can be predicted from plasma concentrations. We concluded that a dosage of 8 mg/kg, SC, every 12 hours would achieve adequate tissue fluid and urine concentrations for susceptible bacteria with a minimum inhibitory concentration of 0.12 µg/mL.

Cortical bone concentrations of enrofloxacin were determined over time in dogs after SC administration of the drug. Nineteen healthy adult dogs were anesthetized and were given 2.5 or 5.0 mg of enrofloxacin/kg of body weight, SC. Serial serum and bone samples were obtained for determination of enrofloxacin concentrations at intervals until 8 hours after drug administration. Cortical bone samples were procured by surgical disarticulation of successive second phalanges. Additional cortical bone samples were taken from long bones in 4 dogs. Mean +/- SD peak serum enrofloxacin concentration was 0.54 +/- 0.10 micrograms/ml for the 2.5-mg/kg dosage and 0.97 +/- 0.34 micrograms/ml for the 5.0-mg/kg dosage. Serum concentration was significantly higher than bone concentration for each dosage. Mean peak bone concentrations reached 29% of peak serum values: 0.15 +/- 0.09 micrograms/g and 0.29 +/- 0.09 micrograms/g for 2.5-mg/kg and 5.0-mg/kg dosages, respectively. Serum concentration for the 5.0-mg/kg dosage was significantly greater than that for the 2.5-mg/kg dosage for all times, whereas bone concentrations for the 5.0-mg/kg dosage were significantly higher at all times after 180 minutes. For the duration of the study, cortical bone concentrations of enrofloxacin at either dosage exceeded the minimum inhibitory concentration (MIC) for the Enterobacteriaceae, but reliably exceeded the MIC for Staphylococcus sp only at the 5.0-mg/kg dosage. At no time did cortical bone concentrations of enrofloxacin exceed the MIC for Pseudomonas aeruginosa at either dosage. To validate extrapolation of data from the second phalanx to long bones and from anesthetized to awake dogs, 16 healthy dogs being euthanatized in unrelated studies were given 2.5 or 5.0 mg of enrofloxacin/kg, sc. These dogs were not anesthetized but were euthanatized at 60, 120, or 240 minutes after drug administration, and multiple cortical bone samples were taken. Antibiotic concentrations in the second phalanx were not significantly different from those in long bones. Comparison of enrofloxacin concentrations in cortical bone of awake and anesthetized dogs suggested no differences between groups. We concluded that general anesthesia and use of the antibiotic concentrations in the second phalanx as representative of those in long bones did not affect results of this study.

Plasma concentration of penicillin G was evaluated in beef steers after administration of either a combination of benzathine penicillin G and procaine penicillin G in a 1:1 mixture at a dosage of 9,000 U/ kg of body weight, IM (n = 5), 24,000 U/kg, IM (n = 5), or 8,800 U/kg, SC (n = 5), or benzathine penicillin G alone at a dosage of 12,000 U/kg, IM (n = 7). Plasma concentration of penicillin G was measured by use of a high-performance liquid chromatography assay that had a limit of determination of 0.005 micrograms/ml. At a dosage for this combination of 9,000 U/kg IM, and 8,800 U/kg, SC, which are approved label recommendations in Canada, and the United States, respectively, mean (+/- SEM) peak plasma concentration was 0.58 (+/- 0.15) and 0.44 (+/- 0.02) micrograms/ml, respectively. Although plasma penicillin concentration was quantifiable for 7 days in the steers that received 9,000 U/kg, IM, and for 4 days in the steers that received 8,800 U/kg, SC, the concentration was < 0.1 micrograms/ml in both groups after the first 12 hours. After administration of the combination at dosage of 24,000 U/kg, IM, there was an initial peak plasma concentration at approximately 2 hours; thereafter, plasma concentration decreased slowly, with half-life of 58 hours. Although plasma penicillin G concentration was quantifiable for 12 days at this dosage, concentration was < 0.1 micrograms/ml after the first 48 hours. After the initial 48 hours, plasma concentration of penicillin was of similar magnitude and decreased at similar rate for the combination at dosage of 24,000 U/ kg and for 12,000 U/kg of benzathine penicillin G alone. Most of the plasma penicillin G concentration in the first 24 hours after administration of a 1:1 combination of benzathine penicillin G and procaine penicillin G is attributable to absorption of procaine penicillin G. After the first 48 hours, most of the plasma drug concentration appeared to be produced by absorption of penicillin G from benzathine penicillin G. Absorption of benzathine penicillin G produces quantifiable plasma penicillin G concentrations for several days, but they are below the level of susceptibility for most bacteria.