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- Author or Editor: Katrina L. Mealey x
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Abstract
Objective—To compare plasma disposition of the R(–) and S(+) enantiomers of carprofen after IV administration of a bolus dose to donkeys and horses.
Animals—5 clinically normal donkeys and 3 clinically normal horses.
Procedure—Blood samples were collected from all animals at time 0 (before) and at 10, 15, 20, 30, and 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 28, 32, and 48 hours after IV administration of a bolus of carprofen (0.7 mg/kg). Plasma was analyzed in triplicate via high-performance liquid chromatography to determine the concentrations of the carprofen enantiomers. A plasma concentration-time curve for each donkey and horse was analyzed separately to estimate noncompartmental pharmacokinetic variables.
Results—In donkeys and horses, the area under the plasma concentration versus time curve (AUC) was greater for the R(–) carprofen enantiomer than it was for the S(+) carprofen enantiomer. For the R(–) carprofen enantiomer, the AUC and mean residence time (MRT) were significantly less and total body clearance (ClT) was significantly greater in horses, compared with donkeys. For the S(+) carprofen enantiomer, AUC and MRT were significantly less and ClT and apparent volume of distribution at steady state were significantly greater in horses, compared with donkeys.
Conclusions and Clinical Relevance—Results have suggested that the dosing intervals for carprofen that are used in horses may not be appropriate for use in donkeys. (Am J Vet Res 2004;65:1479–1482)
Abstract
Objective—To determine whether the reported drug-drug interaction between the flea medication spinosad and ivermectin is attributable to inhibition of P-glycoprotein by spinosad.
Animals—6 healthy adult dogs with the ABCB1 wildtype genotype.
Procedures—The study was conducted as a prospective, masked, randomized crossover design. Six dogs were allocated to 2 groups; each dog served as its own control animal. Dogs in one of the groups received spinosad at the manufacturer's recommended dose; the other group received no treatment. Forty-eight hours later, scintigraphic imaging of the head and abdomen were performed with the radiolabeled P-glycoprotein substrate methoxy-isobutyl-isonitrile (sestamibi) in both groups of dogs. After a washout period of 60 days, the dogs in each group received the alternate treatment, and scintigraphic imaging again was performed 48 hours later. Gallbladder-to-liver and brain-to-neck musculature ratios of technetium Tc 99m sestamibi were calculated for each dog and compared between treatments.
Results—No significant differences in gallbladder-to-liver or brain-to-neck musculature ratios were found between treatments.
Conclusions and Clinical Relevance—Results provided evidence that spinosad did not inhibit P-glycoprotein function 48 hours after spinosad was administered at the manufacturer's recommended dose. Further investigations will be necessary to elucidate the mechanism of the reported toxic interaction between spinosad and ivermectin.
Abstract
Objective—To determine plasma disposition after dermal application of a liposome-encapsulated formulation of lidocaine in cats.
Animals—6 healthy adult cats with a mean (± SD) body weight of 4.1 ± 0.44 kg.
Procedure—CBC determination and biochemical analysis of blood samples were performed for all cats. Cats were anesthetized by use of isoflurane, and catheters were placed IV in a central vein. The next day, blood samples were obtained from the catheters before and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after applying a 4% liposome-encapsulated lidocaine cream (15 mg/kg) to a clipped area over the cephalic vein. Plasma concentrations of lidocaine were analyzed with a high-performance liquid chromatography assay.
Results—Two cats had minimal transdermal absorption of lidocaine, with lidocaine concentrations below the sensitivity of the assay at all but 1 or 2 time points. In the other 4 cats, the median maximum plasma concentration was 149.5 ng/ml, the median time to maximum plasma concentration was 2 hours, and the median area under the concentration versus time curve from zero to infinity was 1014.5 ng·h/ml.
Conclusions and Clinical Relevance—Maximum plasma concentrations of lidocaine remained substantially below toxic plasma concentrations for cats. On the basis of these data, topical administration of a liposome-encapsulated lidocaine formulation at a dose of 15 mg/kg appears to be safe for use in healthy adult cats. (Am J Vet Res 2002;63:1309–1312)
Abstract
Objective—To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species.
Animals—5 clinically normal horses and 5 clinically normal donkeys.
Procedures—Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinetic variables.
Results—In horses and donkeys, mean ± SD area under the curve was 18.8 ± 7.31 μg/mL/h and 4.6 ± 2.55 μg/mL/h, respectively; mean residence time (MRT) was 9.6 ± 9.24 hours and 0.6 ± 0.36 hours, respectively. Total body clearance (CLT) was 34.7 ± 9.21 mL/kg/h in horses and 187.9 ± 147.26 mL/kg/h in donkeys. Volume of distribution at steady state (VDSS) was 270 ± 160.5 mL/kg in horses and 93.2 ± 33.74 mL/kg in donkeys. All values, except VDSS, were significantly different between donkeys and horses.
Conclusions and Clinical Relevance—The small VDSS of meloxicam in horses and donkeys (attributed to high protein binding) was similar to values determined for other nonsteroidal anti-inflammatory drugs. Compared with other species, horses had a much shorter MRT and greater CLT for meloxicam, indicating a rapid elimination of the drug from plasma; the even shorter MRT and greater CLT of meloxicam in donkeys, compared with horses, may make the use of the drug in this species impractical.
Abstract
Objective—To determine the lowest of 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, or 0.01 μg/kg) administered IV that stimulates maximal cortisol secretion in clinically normal dogs.
Animals—10 clinically normal dogs.
Procedures—5 dose-response experiments were performed in each of the dogs. Each dog received 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, and 0.01 μg/kg) IV in random order (2-week interval between each dose). Serum samples for determination of cortisol concentrations were obtained before (baseline) and at 10, 20, 30, 40, 50, 60, 120, and 240 minutes after cosyntropin administration.
Results—Compared with baseline values, mean serum cortisol concentration in the study dogs increased significantly after administration of each of the 5 cosyntropin doses. Mean peak serum cortisol concentration was significantly lower after administration of 0.01, 0.05, and 0.1 μg of cosyntropin/kg, compared with findings after administration of 0.5 and 1.0 μg of cosyntropin/kg. After administration of 0.5 and 1.0 μg of cosyntropin/kg, mean peak serum cortisol concentration did not differ significantly; higher doses of cosyntropin resulted in more sustained increases in serum cortisol concentration, and peak response developed after a longer interval.
Conclusions and Clinical Relevance—Administration of cosyntropin IV at a dose of 0.5 μg/kg induced maximal cortisol secretion in healthy dogs. Serum cortisol concentration was reliably increased in all dogs after the administration of each of the 5 doses of cosyntropin. These data should be useful in subsequent studies to evaluate the hypothalamic-pituitary-adrenal axis in healthy and critically ill dogs.
Abstract
Objective—To compare plasma disposition of alkaloids after lupine challenge in cattle that had given birth to calves with lupine-induced arthrogryposis and cattle that had given birth to clinically normal calves and determine whether the difference in outcome was associated with differences in plasma disposition of anagyrine.
Animals—6 cows that had given birth to calves with arthrogryposis and 6 cows that had given birth to clinically normal calves after being similarly exposed to lupine during pregnancy.
Procedure—Dried lupine (2 g/kg) was administered via gavage. Blood samples were collected before and at various time points for 48 hours after lupine administration. Anagyrine, 5,6-dehydrolupanine, and lupanine concentrations in plasma were measured by use of gas chromatography. Plasma alkaloid concentration versus time curves were generated for each alkaloid, and pharmacokinetic parameters were determined for each cow.
Results—No significant differences in area under the plasma concentration versus time curve, maximum plasma concentration, time to reach maximum plasma concentration, and mean residence time for the 3 alkaloids were found between groups.
Conclusions and Clinical Relevance—Because no differences were found in plasma disposition of anagyrine following lupine challenge between cattle that had given birth to calves with arthrogryposis and those that had not, our findings do not support the hypothesis that between-cow differences in plasma disposition of anagyrine account for within-herd differences in risk for lupine-induced arthrogryposis. (Am J Vet Res 2004;65:1580–1583)
