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D W Upson

Publications and source records attributed to D W Upson.

15 recordsLinked to original sources

Comparative pharmacokinetics of doramectin and ivermectin in cattle.

Plasma pharmacokinetics were compared for 40 cattle dosed by subcutaneous injection with doramectin or ivermectin (200 micrograms kg-1), commercial formulations of doramectin or ivermectin, 20 cattle per product). Doramectin exhibited a similar peak plasma concentration to ivermectin (about 32 ng ml-1), but the time to Cmax was longer for doramectin (5.3 +/- 0.35 days) than for ivermectin (4.0 +/- 0.28 days). The area under the curve from time 0 to infinity post-injection was significantly higher (p < 0.001) for doramectin (511 +/- 16 ng day ml-1) than for ivermectin (361 +/- 17 ng day ml-1). This was explained by a lower clearance, a lower volume of distribution and, probably, a higher bioavailability of doramectin over ivermectin. It is concluded that the pharmacokinetic differences between doramectin and ivermectin may explain the longer duration of preventive efficacy of doramectin.

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Lung tissue concentrations and plasma pharmacokinetics of danofloxacin in calves with acute pneumonia.

Plasma and lung tissue pharmacokinetics of danofloxacin in calves with naturally induced acute pneumonia were determined in 2 separate studies. A maximal pneumonic tissue concentration of 1.17 micrograms/g was achieved 1.8 hours after IM injection of 1.25 mg of danofloxacin/kg of body weight. Pneumonic tissue danofloxacin concentrations were 5.5 times greater than those in plasma at 1 and 2 hours after injection. Cranioventral pneumonic tissue had significantly decreased danofloxacin concentration, compared with that of grossly normal tissue from the caudodorsal part of the lungs at 2 of 6 sample times. After IV injection, the apparent steady-state volume of distribution was 3.44 +/- 1.13 L/kg, and the elimination half-life was 6.26 +/- 2.27 hours. Maximal plasma danofloxacin concentration of 0.25 micrograms/ml was detected 0.80 hour after IM injection. Bioavailability was 91%. Our findings indicated that a large percentage of danofloxacin is rapidly absorbed after IM administration to calves with acute pneumonia. Extensive tissue penetration was suggested by a high steady-state volume of distribution and was indicated by high concentrations in pneumonic tissue.

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Regional danofloxacin lung tissue concentrations and their relationship to regional pulmonary blood flow in consolidated and nonconsolidated bovine lung.

Six calves with areas of pulmonary consolidation attributable to bronchopneumonia, and 6 calves with no areas of consolidation were given i.v. injections of danofloxacin. This injection was followed approximately 55 minutes later by injection of 15-microns radio-labeled microspheres to measure regional pulmonary blood flow. Calves were euthanatized exactly 1 hour after the danofloxacin injection. Six samples for determination of danofloxacin concentration, each surrounded by 4 samples for determination of gamma emission counts, were taken from each lung. Additional samples focusing on the line of demarcation between consolidated and nonconsolidated tissue were taken from calves with pulmonary consolidation. Data from calves with no areas of pulmonary consolidation indicated that blood flow was significantly reduced in the caudodorsal position of the left lung and the caudodorsal and cranioventral positions of the right lungs. Danofloxacin concentrations in the cranioventral positions of the right and left lungs were significantly lower than those in the middle-dorsal positions. Differences in danofloxacin concentrations and blood flow were analyzed in consolidated and non-consolidated cranioventral and middle-ventral positions of the lungs from calves with pulmonary consolidation. Decreases in blood flow in consolidated lung tissue ranged from 83.3 to 91.7%. Danofloxacin concentrations in consolidated lung tissue were significantly reduced by 41% in the middle-ventral position of the left lung. The line of demarcation step study revealed a significant reduction of blood flow at 2 and 4 cm into consolidated lung tissue, with reductions of 84 and 88%, respectively. Danofloxacin concentration did not significantly decrease in consolidated tissue.

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Ruminant pharmacology.

Aspects of drug disposition, metabolism, and toxicity in the ruminant animal are discussed, and illustrative examples are provided. The effects of the reticulo-rumen on drug disposition in the ruminant are highlighted.

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Problems and practice in mass medication of beef cattle.

Mass medication is a health management tool that, when used appropriately, results in cost savings and sound economic return to the food animal producer. Careful planning and consideration should precede the implementation of a mass treatment program, clearly defining the goal to be achieved and a detailed plan of execution. For economic as well as professional reasons, indiscriminate administration of antimicrobials to large groups of food animals should be avoided.

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Oxytetracycline pharmacokinetics, tissue depletion, and toxicity after administration of a long-acting preparation at double the label dosage.

Oxytetracycline (OTC) concentration in plasma and tissues, plasma pharmacokinetics, depletion from tissue, and toxicity were studied in 30 healthy calves after IM administration of a long-acting OTC preparation (40 mg/kg of body weight) at double the label dosage (20 mg/kg). Plasma OTC concentration increased rapidly after drug administration, and by 2 hours, mean (+/- SD) values were 7.4 +/- 2.6 micrograms/ml, Peak plasma OTC concentration was 9.6 +/- 2.6 micrograms/ml, and the time to peak plasma concentration was 7.6 +/- 4.0 hours. Plasma OTC concentration decreased slowly for 168 hours (elimination phase) after drug administration, and the elimination half-life was 23.9 hours. Plasma OTC concentration exceeded 3.8 micrograms/ml at 48 hours after drug administration. From 168 to 240 hours after drug administration, plasma OTC concentration decreased at a slower rate than that seen during the elimination phase. This slower phase was termed the depletion phase, and the depletion half-life was 280.7 hours. Tissue OTC concentration was highest in kidneys and liver. Lung OTC concentration exceeded 4.4 micrograms/g of tissue and 2.0 micrograms/g of tissue at 12 and 48 hours after drug administration, respectively. The drug persisted the longest in kidneys and liver. At 42 days after drug administration, 0.1 micrograms of OTC/g of kidney was detected. At 49 days after drug administration, all OTC tissue concentrations were below the detectable limit. Reactions and toxicosis after drug administration were limited to an anaphylaxis-like reaction (n = 1) and injection site swellings (n = 2).

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Factors affecting the accuracy of the live animal swab test for detecting urine oxytetracycline and predicting oxytetracycline residues in calves.

The live animal swab test (LAST) was compared with quantitative oxytetracycline (OTC) assay of urine samples and tissue specimens to determine the accuracy of the LAST in detecting OTC in bovine urine and predicting violative residues in tissues. When urine OTC concentration was greater than 4.3 micrograms/ml, the LAST result was 100% accurate. When urine OTC concentration was less than 4.3 micrograms/ml, the LAST result was 60% accurate; 20% of the LAST results were false-positive, and 20% were false-negative. Urine osmolarity was highest (P less than 0.05) in samples with false-positive results and lowest (P less than 0.05) in samples with false-negative results. A similar trend was observed for urine pH, but was not statistically significant. Urine samples with false-positive results apparently had osmolarity and pH conditions that inhibited growth of Bacillus subtilis when OTC was lacking. False-negative results probably were obtained because urine osmolarity and pH conditions were favorable for the growth of bacteria even in the presence of OTC or because OTC concentration was below the limit of detection by the LAST. The LAST was inconsistent in detecting urine OTC in small concentrations and correspondingly failed to accurately predict OTC residues in tissues.

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Therapeutic and toxic plasma concentrations of digoxin in the cat.

Nonanesthetized cats of both sexes were given oral digoxin (0.011 mg/kg of body weight) 3 forms: elixir, tablet, and crushed tablet mixed with food. Mean peak plasma concentrations of digoxin were highest with the elixir (1.89 +/- 1.02 ng/ml) and lowest with the crushed tablet mixed with food (0.66 +/- 0.35 ng/ml). Male cats had significantly higher (P less than 0.10) mean plasma digoxin concentrations than did female cats. A 2nd group of nonanesthetized cats of both sexes was given digoxin elixir orally at therapeutic amounts (0.011 mg/kg) once a day for 4 consecutive days. The cumulative effect of digoxin resulted in 62% increase in the mean peak plasma concentration and 231% increase in the 24-hour plasma concentration of digoxin over the 4-day period. Male cats had a significantly (P less than 0.05) higher mean plasma digoxin concentration than did the female cats. Significant changes in the ECG were not recorded. A 3rd group of nonanesthetized cats of both sexes was given a single toxic dose (0.11 mg/kg) of digoxin elixir orally. All cats showed clinical signs of digitalis toxicosis (depression, vomiting, salivation, and anorexia) before ECG changes appeared. Alterations in the ECG were minimal; the most important changes were a slight increase in the PQ interval, an elevated ST segment, and decreased heart rate. Plasma concentrations of digoxin at the time of vomition ranged from 4.45 to 12.12 ng/ml with a mean peak plasma value of 7.37 +/- 3.61 ng/ml. The cats were clinically ill for 48 to 96 hours. A plasma digoxin concentration of 2.3 ng/ml was not toxic.

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Bile flow and electrolyte composition of bile associated with maximum bilirubin excretion in sheep.

Changes in the composition of bile accompanying the maximum biliary excretion (Emax) of bilirubin were investigated in sheep. Sheep fitted with chronic 'T-tubes' in the common bile duct were infused with taurocholate and bilirubin at various rates. Bile collected during both pre- and post-bilirubin steady-state periods was analyzed for the biliary concentration of electrolytes, bile salts, and bilirubin. Bilirubin Emax was 24.6 mumol/min while bile salt excretion during this period was 103 mumol/min. At Emax bilirubin entry into bile reached a concentration of 16.1 mumol/mL, increased the biliary concentration of sodium, did not change osmolarity of bile, and did not increase bile flow. The data suggest that bilirubin either interacts with mixed micelles in bile or forms molecular aggregates.

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