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- Author or Editor: Ronald Gronwall x
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SUMMARY
Three sets of paired circular and square full-thickness skin wounds were made on the dorsum of the metacarpus (n = 48) of 8 horses. Each wound was 6.25 cm2 in area. The wounds were treated topically with an ointment, nonadherent dressing, and bandaged with a snug elastic wrap. Wounds were photographed every other day until healing was complete. Wound areas were measured and exponential and linear wound healing models were applied to the wound healing data generated. Wound healing variables measured for each wound were: number of days to healing, maximal size attained, rate of wound contraction (calculated by use of first-order and linear models), final wound size, and percentage of wound that healed by contraction.
The exponential model fit the data significantly better than the linear model. The maximal size attained by circular wounds was significantly smaller than the maximal size attained by square wounds. Wound shape did not influence the rate of wound healing. On the basis of our findings, conversion of circular defects to square defects would not speed wound healing.
Summary
Five healthy adult mares and 1 gelding were given a single dose (15 mg/kg of body weight) of metronidazole per rectum. After manual evacuation of feces from the rectum, a suspension of crushed tablets and water (40 ml) was administered via a 28-F catheter advanced 30 cm into the rectum. Blood samples were obtained by jugular venipuncture, and metronidazole concentration was measured serially for the 14 hours after drug administration. Mean serum concentration of metronidazole peaked at 4.5 μg/ml, 0.83 hour after administration, and decreased to 0.38 μg/ml, 14 hours after administration. Mean elimination rate constant was 0.23/h, and the harmonic mean elimination half-life was 3.04 hours. Further study is necessary to determine a therapeutic dose regimen for metronidazole administered per rectum.
Summary
Each of 5 healthy mares was given 5 consecutive im injections of ceftiofur sodium (2 mg/kg of body weight; 50 mg/ml) at 12-hour intervals. Ceftiofur concentrations were measured serially in serum, synovial fluid, peritoneal fluid, and urine, and were measured in CSF and endometrial tissue after the fifth dose. Mean elimination rate constant was 0.354 ± 0.101 h−1 and elimination half-life was 2.49 ± 0.49 hour. Mean serum ceftiofur concentrations peaked approximately 1 hour after each injection. The highest mean ceftiofur concentration was 5.09 μg/ml at 1 hour after the fifth dose for serum, 3.02 μg/ml at 2 hours after the fifth dose for synovial fluid, and 3.23 μg/ml at 4 hours after the fifth dose for peritoneal fluid. Mean urine concentrations reached 15.72 μg/ml at 1 hour after the fifth dose. Ceftiofur was not detected in csf or endometrial tissue. None of the mares had adverse reactions to the drug.
Summary
Pharmacokinetic values for flunixin meglumine (1 mg/kg of body weight) and phenylbutazone (4 mg/kg) dosages were determined after a single iv injection with and without concurrent intragastric administration of probenecid (50 mg/kg) in 6 healthy mares. Significant difference was not apparent in the pharmacokinetic values of flunixin meglumine with and without concurrent probenecid administration. Significant (P ≤ 0.05) increase was evident in the 12-hour mean concentration of phenylbutazone (11.45 ± 1.66 μg/ml without probenecid; 14.56 ± 1.20 μg/ml with probenecid) along with significant (P ≤ 0.05) reduction in its volume of distribution at steady state associated with concurrent probenecid administration (218.6 ± 11.52 ml/kg without probenecid; 169.4 ± 9.25 ml/kg with probenecid).
Abstract
Objective—To determine the pharmacokinetics of azithromycin and its concentration in body fluids and bronchoalveolar lavage cells in foals.
Procedure—Azithromycin (10 mg/kg of body weight) was administered to each foal via IV and intragastric (IG) routes in a crossover design. After the first IG dose, 4 additional IG doses were administered at 24-hour intervals. A microbiologic assay was used to measure azithromycin concentrations in serum, peritoneal fluid, synovial fluid, pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells.
Results—Azithromycin elimination half-life was 20.3 hours, body clearance was 10.4 ml/min·kg, and apparent volume of distribution at steady state was 18.6 L/kg. After IG administration, time to peak serum concentration was 1.8 hours and bioavailability was 56%. After repeated IG administration, peak serum concentration was 0.63 ± 0.10 µg/ml. Peritoneal and synovial fluid concentrations were similar to serum concentrations. Bronchoalveolar cell and PELF concentrations were 15- to 170-fold and 1- to 16-fold higher than concurrent serum concentrations, respectively. No adverse reactions were detected after repeated IG administration.
Conclusions and Clinical Relevance—On the basis of pharmacokinetic values, minimum inhibitory concentrations of Rhodococcus equi isolates, and drug concentrations in PELF and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate. (Am J Vet Res 2001;62:1870–1875)
Abstract
Objective—To determine the disposition of orally administered cefpodoxime proxetil in foals and adult horses and measure the minimum inhibitory concentrations (MICs) of the drug against common bacterial pathogens of horses.
Animals—6 healthy adult horses and 6 healthy foals at 7 to 14 days of age and again at 3 to 4 months of age.
Procedure—A single dose of cefpodoxime proxetil oral suspension was administered (10 mg/kg) to each horse by use of a nasogastric tube. In 7- to 14-day-old foals, 5 additional doses were administered intragastrically at 12-hour intervals. The MIC of cefpodoxime for each of 173 bacterial isolates was determined by use of a commercially available test.
Results—In 7- to 14-day-old foals, mean ± SD time to peak serum concentration (Tmax) was 1.7 ± 0.7 hours, maximum serum concentration (Cmax) was 0.81 ± 0.22 µg/mL, and elimination half-life (harmonic mean) was 7.2 hours. Disposition of cefpodoxime in 3- to 4-month-old foals was not significantly different from that of neonates. Adult horses had significantly higher Cmax and significantly lower Tmax, compared with values for foals. The MIC of cefpodoxime required to inhibit growth of 90% of isolates for Salmonella enterica, Escherichia coli, Pasteurella spp, Klebsiella spp, and β-hemolytic streptococci was 0.38, 1.00, 0.16, 0.19, and 0.09 µg/mL, respectively.
Conclusions and Clinical Relevance—Oral administration at a dosage of 10 mg/kg every 6 to 12 hours would appear appropriate for the treatment of equine neonates with bacterial infections. (Am J Vet Res 2005;66:30–35)
Abstract
Objective—To determine whether plasma concentrations of benzodiazepines (BDZ) in dogs following intranasal (IN) administration of diazepam are comparable to concentrations following IV administration.
Animals—6 (4 male, 2 female) healthy adult Greyhounds.
Procedure—Dogs were randomly assigned to 2 groups of 3 dogs in a crossover design. Diazepam (0.5 mg/kg of body weight) was administered intravenously to dogs in group 1 and intranasally to dogs in group 2. Blood was collected from the jugular vein of each dog into tubes containing lithium heparin before and 3, 6, 9, 12, 15, 20, 30, 60, 120, 240, and 480 minutes following diazepam administration. After a 4-day washout period, dogs in group 1 received diazepam intranasally, dogs in group 2 received diazepam intravenously, and blood was again collected. Plasma concentration of BDZ was determined by use of a fluorescence polarization immunoassay.
Results—Mean (± SD) peak plasma concentration of BDZ following IV administration (1316 ± 216 µg/L) was greater than that following IN administration (448 ± 41 µg/L). Time to peak concentration was ≤ 3 minutes following IV administration and 4.5 ± 1.5 minutes following IN administration. Mean bioavailability of BDZ following IN administration was 80 ± 9%.
Conclusions and Clinical Relevance—Diazepam is rapidly and efficiently absorbed following IN administration of the parenteral formulation. Plasma concentrations match or exceed the suggested therapeutic concentration (300 µg/L). Intranasal administration of diazepam may be useful for treatment of seizures in dogs by owners or when intravenous access is not readily available. (Am J Vet Res 2000;61:651–654)
Summary
Six healthy adult mixed breed dogs were each given 5 oral doses of trimethoprim (TMP)/sulfadiazine (sdz) at 2 dosage regimens: 5 mg of TMP/kg of body weight and 25 mg of SDZ/kg every 24 hours (experiment 1) and every 12 hours (experiment 2). Serum and skin concentrations of each drug were measured serially throughout each experiment and mean serum concentrations of tmp and sdz were determined for each drug for 24 hours (experiment 1) and 12 hours (experiment 2) after the last dose was given. In experiment 1, mean serum tmp concentration was 0.67 ± 0.02 μg/ml, and mean skin tmp concentration was 1.54 ± 0.40μg/g. Mean serum sdz concentration was 51.1 ± 12.2 μg/ml and mean skin sdz concentration was 59.3 ± 9.8 μg/g. In experiment 2, mean serum tmp concentration was 1.24 ± 0.35 μg/ml and mean skin tmp concentration was 3.03 ± 0.54 μg/g. Mean serum SDZ concentration was 51.6 ± 9.3 μg/ml and mean skin sdz concentration was 71.1 ± 8.2 μg/g. After the 5th oral dose in both experiments, mean concentration of tmp and sdz in serum and skin exceeded reported minimal inhibitory concentrations of tmp/sdz (≤ 0.25/4.75 μg/ml) for coaguase-positive Staphylococcus sp. It was concluded that therapeutically effective concentrations in serum and skin were achieved and maintained when using the manufacturer’s recommended dosage of 30 mg of tmp/sdz/kg (5 mg of TMP/kg and 25 mg of sdz/kg) every 24 hours.
SUMMARY
Serum concentrations of metronidazole were determined in 6 healthy adult mares after a single iv injection of metronidazole (15 mg/kg of body weight). The mean elimination rate (K) was 0.23 h-1, and the mean elimination half-life (t1/2) was 3.1 hours. The apparent volume of distribution at steady state was 0.69 L/kg, and the clearance was 168 ml/h/kg.
Each mare was then given a loading dose (15 mg/kg) of metronidazole at time 0, followed by 4 maintenance doses (7.5 mg/kg, q 6 h) by nasogastric tube. Metronidazole concentrations were measured in serial samples of serum, synovia, peritoneal fluid, and urine. Metronidazole concentrations in csf and endometrial tissues were measured after the fourth maintenance dose. The highest mean concentration in serum was 13.9 ± 2.18 μg/ml at 40 minutes after the loading dose (time 0). The highest mean synovial and peritoneal fluid concentrations were 8.9 ± 1.31 μg/ml and 12.8 ± 3.21 μg/ml, respectively, 2 hours after the loading dose. The lowest mean trough concentration in urine was 32 μg/ml. Mean concentration of metronidazole in csf was 4.3 ± 2.51 μg/ml and the mean concentration in endometrial tissues was 0.9 ± 0.48 μg/g at 3 hours after the fourth maintenance dose.
Two mares hospitalized for treatment of bacterial pleuropneumonia were given metronidazole (15.0 mg/kg, po, initially then 7.5 mg/kg, po, q 6 h), while concurrently receiving gentamicin, potassium penicillin, and flunixin meglumine iv. Metronidazole pharmacokinetics and serum concentrations in the sick mares were similar to those obtained in the healthy mares.
Summary
Six calves with suppurative arthritis were given a single im injection of sodium cephapirin at a dosage of 10 mg/kg of body weight. Cephapirin concentrations were serially measured in serum and in normal and suppurative synovial fluid over a 24-hour period. Mean peak serum concentration was 6.33 μl/ml at 20 minutes after injection. The highest cephapirin concentrations in normal and suppurative synovial fluid were 1.68 and 1.96 μg/ml, respectively, 30 minutes after injection. Overall mean cephapirin concentration in normal synovial fluid for the first 4 hours (1.04 ± 0.612 μg/ml) was not significantly different from that in suppurative synovial fluid (0.88 ± 0.495 μg/ml; P > 0.05). Elimination half-life was 0.60 hours and clearance was 1,593 ml/h/kg.
